Co-reporter:Yu Chong, Cuicui Ge, Ge Fang, Renfei Wu, He Zhang, Zhifang Chai, Chunying Chen, and Jun-Jie Yin
Environmental Science & Technology September 5, 2017 Volume 51(Issue 17) pp:10154-10154
Publication Date(Web):August 3, 2017
DOI:10.1021/acs.est.7b00663
Before graphene derivatives can be exploited as next-generation antimicrobials, we must understand their behavior under environmental conditions. Here, we demonstrate how exposure to simulated sunlight significantly enhances the antibacterial activity of graphene oxide (GO) and reveal the underlying mechanism. Our measurements of reactive oxygen species (ROS) showed that only singlet oxygen (1O2) is generated by GO exposed to simulated sunlight, which contributes only slightly to the oxidation of antioxidant biomolecules. Unexpectedly, we find the main cause of oxidation is light-induced electron–hole pairs generated on the surface of GO. These light-induced electrons promote the reduction of GO, introducing additional carbon-centered free radicals that may also enhance the antibacterial activities of GO. We conclude that GO-mediated oxidative stress mainly is ROS-independent; simulated sunlight accelerates the transfer of electrons from antioxidant biomolecules to GO, thereby destroying bacterial antioxidant systems and causing the reduction of GO. Our insights will help support the development of graphene for antibacterial applications.
Co-reporter:Xinyi Wang, Mingzhe Wang, Rong Lei, Shui Fang Zhu, Yuliang Zhao, and Chunying Chen
ACS Nano May 23, 2017 Volume 11(Issue 5) pp:4606-4606
Publication Date(Web):May 1, 2017
DOI:10.1021/acsnano.7b00200
When nanoparticles are exposed to a physiological environment, a “protein corona” is formed that greatly determines their biological fate. Adsorption of proteins could be influenced by chiral surfaces of nanoparticles; however, very few quantitative studies are available on the interaction of protein with the chiral surface of nanoparticles, and the underlying mechanism remains largely unresolved. We have developed a strategy to quantitatively analyze the adsorption and conformational features of transferrin on gold nanoparticles that are functionalized with d, l, and racemic penicillamine. We used a quartz microbalance platform to monitor the interaction of the adsorbed transferrin with transferrin receptors in HEK cell-derived liposomes. Results show that the chiral surface of nanoparticle determines the orientation and conformation of transferrin, which subsequently affects the interaction and recognition of transferrin with its receptor on the cellular membrane. Transferrin is widely used as a tumor-targeting ligand in cancer treatment and diagnosis since the transferrin receptor is overexpressed on the cell membrane of various types of cancer cells. Thus, the present results will help to expand the knowledge on biological identity of nanoparticles with chiral surfaces in a physiological environment and provide an insight into the rational design of therapeutic nanoparticles.Keywords: chirality; gold nanoparticles; nanobiological effects; protein corona; transferrin;
Co-reporter:Jinglong Tang, Huige Zhou, Jiaming Liu, Jing Liu, Wanqi Li, Yuqing Wang, Fan Hu, Qing Huo, Jiayang Li, Ying Liu, and Chunying Chen
ACS Applied Materials & Interfaces July 19, 2017 Volume 9(Issue 28) pp:23497-23497
Publication Date(Web):June 29, 2017
DOI:10.1021/acsami.7b06393
Cancer stem cells (CSCs) have been identified as a new target for therapy in diverse cancers. Traditional therapies usually kill the bulk of cancer cells, but are often unable to effectively eliminate CSCs, which may lead to drug resistance and cancer relapse. Herein, we propose a novel strategy: fabricating multifunctional magnetic Fe3O4@PPr@HA hybrid nanoparticles and loading it with the Notch signaling pathway inhibitor N-[N-(3,5-difluorophenacetyl-l-alanyl)]-S-phenylglycinet-butylester (DAPT) to eliminate CSCs. Hyaluronic acid ligands greatly enhance the accumulation of the hybrid nanoparticles in the tumor site and in the CSCs. Both hyaluronase in the tumor microenvironment and the magnetic hyperthermia effect of the inner magnetic core can accelerate the release of DAPT. This controlled release of DAPT in the tumor site further enhances the ability of the combination of chemo- and magnetohyperthermia therapy to eliminate cancer stem cells. With the help of polypyrrole-mediated photoacoustic and Fe3O4-mediated magnetic resonance imaging, the drug release can be precisely monitored in vivo. This versatile nanoplatform enables effective elimination of the cancer stem cells and monitoring of the drugs.Keywords: cancer stem cells; DAPT; Fe3O4@PPr@HA hybrid nanoparticles; magnetic resonance imaging; photoacoustic imaging;
Co-reporter:Xiaoyang Hou, Huige Zhou, Liming Wang, Jianqin Tang, Chunying Chen, Guan Jiang, Yanqun Liu
Cancer Letters 2017 Volume 390(Volume 390) pp:
Publication Date(Web):1 April 2017
DOI:10.1016/j.canlet.2016.12.026
•The nanoparticles IR820-CS-Fe3O4 have good stability in aqueous solution even for 8 days.•They have insignificant cytotoxicity on cell viability.•An outstanding T1/T2 MR imaging ability of IR820-CS-Fe3O4 nanoparticles was achieved.•The nanoparticles present an obvious killing effect on A375 cells after irradiation under NIR laser.Theranostics based on nanoparticles have developed rapidly in the past decade and have been widely used in the diagnosis and treatment of liver cancer, breast cancer, and other tumors. However, for skin cancers, there are limited studies. In the present study, we successfully synthesized a theranostic nanoparticle by grating IR820 onto the surface of chitosan-coated magnetic iron oxide, IR820-CS-Fe3O4, showing an excellent magnetic resonance imaging (MRI) capability and cytotoxic effects against melanoma under irradiation with a near-infrared (NIR) laser (808 nm) in vitro. Furthermore, good stability for up to 8 days and negligible cytotoxicity were observed. These characteristics are important for biomedical applications of nanoparticles. In conclusion, we provide a novel and potential theranostic platform for melanoma treatment and detection.
Co-reporter:Mengyu Guo, Shuying Bi, Jing Liu, Wenshi Xu, ... Chunying Chen
Chinese Chemical Letters 2017 Volume 28, Issue 9(Volume 28, Issue 9) pp:
Publication Date(Web):1 September 2017
DOI:10.1016/j.cclet.2017.07.021
Environmental stress factors could lead to the excess generation of reactive oxygen species (ROS) that induces various forms of skin damage related to oxidative stress. Polyhydroxylated fullerene derivative C60(OH)n, acting as an effective agent for prevention of skin aging, is widely used in the lotion and sunscreens in the field of cosmetics, but rarely used in the masks. In this study, we prepared C60(OH)n-loaded nanofibrous membranes to protect human keratinocyte cells from ROS-associated damage and suppress the elevation of intracellular ROS and Ca2+ along with the apoptotic cell death. Two FDA-approved biodegradable polymers, PLGA and PCL, have been used for making the electrospun nanofibers, with C60(OH)n added to the polymers as an antioxidant. The nanofibrous membranes with good biocompatibility might be potentially applied in clinical practice to reduce skin aging.C60(OH)n-loaded nanofibrous membranes were prepared by electrospinning to suppress the elevation of intracellular ROS and Ca2+, and to protect human keratinocyte cells from ROS-associated damage and apoptosis.Download high-res image (176KB)Download full-size image
Co-reporter:Huige Zhou;Jinglong Tang;Jiayang Li;Wanqi Li;Ying Liu
Nanoscale (2009-Present) 2017 vol. 9(Issue 9) pp:3040-3050
Publication Date(Web):2017/03/02
DOI:10.1039/C7NR00089H
Surface ligands and their densities may significantly influence the optic, electric, and stable properties of inorganic nanoparticles as well as their magnetic resonance imaging (MRI) characters. In this study, ultra-small iron oxide nanoparticles with hyaluronic acid as surface ligand (Fe3O4@HA) were designed to target tumor cells and tune the T1- and T2-weighted MRI by aggregating in the tumor microenvironment via the degradation of HA upon exposure to hyaluronidase (HAase) with decreasing pH. To realize this purpose, four kinds of Fe3O4@HA nanoparticles with increasing HA density were synthesized and characterized. Fe3O4@HA280, with higher r1 value than others, was chosen for the signal modulation test in vitro; the T2 signal was enhanced by 36%, and the T1 signal decreased by 22% in the presence of HAase and acidic environment during the measurement. However, the chitosan-coated Fe3O4 nanoparticles did not show a similar tendency. The overlapping sections in the signal change graph of MDA-MB-231 cells and tumor-bearing mice also validate the self-assembling ability of Fe3O4@HA280. Meanwhile, the tumor mapping graphs indicate the excellent tumor penetration of Fe3O4@HA280, which facilitates this self-assembly process and enhances the interior section contrast of the tumor. This fundamental technique for tuning magnetic properties by the tumor microenvironment may provide a useful strategy for the rational synthesis of other inorganic nanoparticles in the field of tumor diagnostics and therapy.
Co-reporter:Rong Cai, Chunying Chen
Science Bulletin 2017 Volume 62, Issue 14(Volume 62, Issue 14) pp:
Publication Date(Web):30 July 2017
DOI:10.1016/j.scib.2017.07.002
Co-reporter:Jiangfeng Du;Zhanjun Gu;Liang Yan;Yuan Yong;Xuan Yi;Xiao Zhang;Jing Liu;Renfei Wu;Cuicui Ge;Yuliang Zhao
Advanced Materials 2017 Volume 29(Issue 34) pp:
Publication Date(Web):2017/09/01
DOI:10.1002/adma.201701268
The development of a new generation of nanoscaled radiosensitizers that can not only enhance radiosensitization of tumor tissues, but also increase radioresistance of healthy tissue is highly desirable, but remains a great challenge. Here, this paper reports a new versatile theranostics based on poly(vinylpyrollidone)- and selenocysteine-modified Bi2Se3 nanoparicles (PVP-Bi2Se3@Sec NPs) for simultaneously enhancing radiotherapeutic effects and reducing the side-effects of radiation. The as-prepared nanoparticles exhibit significantly enhanced free-radical generation upon X-ray radiation, and remarkable photothermal effects under 808 nm NIR laser irradiation because of their strong X-ray attenuation ability and high NIR absorption capability. Moreover, these PVP-Bi2Se3@Sec NPs are biodegradable. In vivo, part of selenium can be released from NPs and enter the blood circulation system, which can enhance the immune function and reduce the side-effects of radiation in the whole body. As a consequence, improved superoxide dismutase and glutathione peroxidase activities, promoted secretion of cytokines, increased number of white blood cell, and reduced marrow DNA suppression are found after radiation treatment in vivo. Moreover, there is no significant in vitro and in vivo toxicity of PVP-Bi2Se3@Sec NPs during the treatment, which demonstrates that PVP-Bi2Se3@Sec NPs have good biocompatibility.
Co-reporter:Huige Zhou, Xiaoyang Hou, Ying Liu, Tianming Zhao, Qiuyu Shang, Jinglong Tang, Jing Liu, Yuqing Wang, Qiuchi Wu, Zehao Luo, Hui Wang, and Chunying Chen
ACS Applied Materials & Interfaces 2016 Volume 8(Issue 7) pp:4424
Publication Date(Web):January 29, 2016
DOI:10.1021/acsami.5b11308
Near-infrared (NIR) dyes functionalized magnetic nanoparticles (MNPs) have been widely applied in magnetic resonance imaging (MRI), NIR fluorescence imaging, drug delivery, and magnetic hyperthermia. However, the stability of MNPs and NIR dyes in water is a key problem to be solved for long-term application. In this study, a kind of superstable iron oxide nanoparticles was synthesized by a facile way, which can be used as T1 and T2 weighted MRI contrast agent. IR820 was grafted onto the surface of nanoparticles by 6-amino hexanoic acid to form IR820-CSQ-Fe conjugates. Attached IR820 showed increased stability in water at least for three months and an enhanced ability of singlet oxygen production of almost double that of free dyes, which will improve its efficiency for photodynamic therapy. Meanwhile, the multispectral optoacoustic tomography (MSOT) and NIR imaging ability of IR820-CSQ-Fe will greatly increase the accuracy of disease detection. All of these features will broaden the application of this material as a multimodal theranostic platform.Keywords: enhanced photodynamic therapy; magnetic nanoparticles; multimodal imaging; NIR dyes; stability
Co-reporter:Rui Chen, Lin Zhao, Ru Bai, Ying Liu, Liping Han, Zhifang Xu, Feng Chen, Herman Autrup, Dingxin Long and Chunying Chen
Toxicology Research 2016 vol. 5(Issue 2) pp:602-608
Publication Date(Web):15 Jan 2016
DOI:10.1039/C5TX00464K
Concerns have arisen about the health and environmental impacts of the increasing commercial use of silver nanoparticles (AgNPs). However, the toxic mechanisms and target tissues of AgNPs have not been fully defined. In this paper, we investigated the tissue toxicity of mice after intravenous administration of AgNPs at a single-dose of 0.2, 2 or 5 mg per kg (body weight), respectively. Biodistribution, endoplasmic reticulum stress, and oxidative stress were examined in mouse organs at eight hours after exposure. Stress markers, e.g. HSP70, BIP, p-IRE1, p-PERK, chop and xbp-1s proteins/genes, were significantly upregulated in a dose-dependent manner. In the liver, spleen, lung and kidney, high stress accompanied by apoptosis occurred. Low stress levels were observed in the heart and brain. Thus, it is proposed that the liver, spleen, lung and kidney are dominant target tissues of AgNP exposure. The lower stress and toxicity in the heart and brain were in agreement with lower AgNP accumulation. The present results demonstrated that AgNP exposure eventually resulted in permanent toxic damage by gradually imposing stress impacts on target organs. These findings highlight the potent applications of stress markers in future risk evaluation of silver nanoparticle toxicity.
Co-reporter:Yang Li, Jinglong Tang, Dong-Xu Pan, Ling-Dong Sun, Chunying Chen, Ying Liu, Ye-Fu Wang, Shuo Shi, and Chun-Hua Yan
ACS Nano 2016 Volume 10(Issue 2) pp:2766
Publication Date(Web):January 21, 2016
DOI:10.1021/acsnano.5b07873
Upconversion (UC) luminescent lanthanide nanoparticles (LNPs) are expected to play an important role in imaging and photodynamic therapy (PDT) in vitro and in vivo. However, with the absorption of UC emissions by photosensitizers (PSs) to generate singlet oxygen (1O2) for PDT, the imaging signals from LNPs are significantly weakened. It is important to activate another imaging route to track the location of the LNPs during PDT process. In this work, Nd3+-sensitized LNPs with dual-band visible and near-infrared (NIR) emissions under single 808 nm excitation were reported to address this issue. The UC emissions in green could trigger covalently linked rose bengal (RB) molecules for efficient PDT, and NIR emissions deriving from Yb3+ and magnetic resonance imaging (MRI) were used for imaging simultaneously. Notably, the designed therapeutic platform could further effectively avoid the overheating effect induced by the laser irradiation, due to the minimized absorption of biological media at around 808 nm. TdT-mediated dUTP nick end labeling (TUNEL) assay showed serious cell apoptosis in the tumor after PDT for 2 weeks, leading to an effective tumor inhibition rate of 67%. Benefit from the PDT, the tumor growth-induced liver and spleen burdens were largely attenuated, and the liver injury was also alleviated. More importantly, pulmonary and hepatic tumor metastases were significantly reduced after PDT. The Nd3+-sensitized LNPs provide a multifunctional nanoplatform for NIR light-assisted PDT with minimized heating effect and an effective inhibition of tumor growth and metastasis.Keywords: Nd3+-sensitized lanthanide nanoparticles; NIR imaging; photodynamic therapy; tumor metastasis; upconversion emissions;
Co-reporter:Jing Liu, Pengyang Wang, Xiao Zhang, Liming Wang, Dongliang Wang, Zhanjun Gu, Jinglong Tang, Mengyu Guo, Mingjing Cao, Huige Zhou, Ying Liu, and Chunying Chen
ACS Nano 2016 Volume 10(Issue 4) pp:4587
Publication Date(Web):March 25, 2016
DOI:10.1021/acsnano.6b00745
A key challenge for the use of inorganic nanomedicines in clinical applications is their long-term accumulation in internal organs, which raises the common concern of the risk of adverse effects and inflammatory responses. It is thus necessary to rationally design inorganic nanomaterials with proper accumulation and clearance mechanism in vivo. Herein, we prepared ultrasmall Cu3BiS3 nanodots (NDs) as a single-phased ternary bimetal sulfide for photothermal cancer therapy guided by multispectral optoacoustic tomography (MSOT) and X-ray computed tomography (CT) due to bismuth’s excellent X-ray attenuation coefficient. We then monitored and investigated their absorption, distribution, metabolism, and excretion. We also used CT imaging to demonstrate that Cu3BiS3 NDs can be quickly removed through renal clearance, which may be related to their small size, rapid chemical transformation, and degradation in an acidic lysosomal environment as characterized by synchrotron radiation-based X-ray absorption near-edge structure spectroscopy. These results reveal that Cu3BiS3 NDs act as a simple but powerful “theranostic” nanoplatform for MSOT/CT imaging-guided tumor ablation with excellent metabolism and rapid clearance that will improve safety for clinical applications in the future.Keywords: chemical transformation; clearance; Cu3BiS3 nanodots; degradation; multispectral optoacoustic tomography; photothermal therapy; X-ray computed tomography
Co-reporter:Yu Chong, Cuicui Ge, Ge Fang, Xin Tian, Xiaochuan Ma, Tao Wen, Wayne G. Wamer, Chunying Chen, Zhifang Chai, and Jun-Jie Yin
ACS Nano 2016 Volume 10(Issue 9) pp:8690
Publication Date(Web):September 1, 2016
DOI:10.1021/acsnano.6b04061
Graphene quantum dots (GQDs), zero-dimensional carbon materials displaying excellent luminescence properties, show great promise for medical applications such as imaging, drug delivery, biosensors, and novel therapeutics. A deeper understanding of how the properties of GQDs interact with biological systems is essential for these applications. Our work demonstrates that GQDs can efficiently scavenge a number of free radicals and thereby protect cells against oxidative damage. However, upon exposure to blue light, GQDs exhibit significant phototoxicity through increasing intracellular reactive oxygen species (ROS) levels and reducing cell viability, attributable to the generation of free radicals under light excitation. We confirm that light-induced formation of ROS originates from the electron–hole pair and, more importantly, reveal that singlet oxygen is generated by photoexcited GQDs via both energy-transfer and electron-transfer pathways. Moreover, upon light excitation, GQDs accelerate the oxidation of non-enzymic anti-oxidants and promote lipid peroxidation, contributing to the phototoxicity of GQDs. Our results reveal that GQDs can display both anti- and pro-oxidant activities, depending upon light exposure, which will be useful in guiding the safe application and development of potential anticancer/antibacterial applications for GQDs.Keywords: anti-oxidants; free radicals; graphene quantum dots; lipid peroxidation; phototoxicity
Co-reporter:Cuicui Ge, Ge Fang, Xiaomei Shen, Yu Chong, Wayne G. Wamer, Xingfa Gao, Zhifang Chai, Chunying Chen, and Jun-Jie Yin
ACS Nano 2016 Volume 10(Issue 11) pp:10436
Publication Date(Web):November 7, 2016
DOI:10.1021/acsnano.6b06297
To develop nanomaterials as artificial enzymes, it is necessary to better understand how their physicochemical properties affect their enzyme-like activities. Although prior research has demonstrated that nanomaterials exhibit tunable enzyme-like activities depending on their size, structure, and composition, few studies have examined the effect of surface facets, which determine surface energy or surface reactivity. Here, we use electron spin-resonance spectroscopy to report that lower surface energy {111}-faceted Pd octahedrons have greater intrinsic antioxidant enzyme-like activity than higher surface energy {100}-faceted Pd nanocubes. Our in vitro experiments found that those same Pd octahedrons are more effective than Pd nanocubes at scavenging reactive oxygen species (ROS). Those reductions in ROS preserve the homogeneity of mitochondrial membrane potential and attenuate damage to important biomolecules, thereby allowing a substantially higher number of cells to survive oxidative challenges. Our computations of molecular mechanisms for the antioxidant activities of {111}- and {100}-faceted Pd nanocrystals, as well as their activity order, agree well with experimental observations. These findings can guide the design of antioxidant-mimicking nanomaterials, which could have therapeutic or preventative potential against oxidative stress related diseases.Keywords: antioxidants; computational chemistry; enzyme-like activity; oxidative stress; palladium nanocrystals; surface facet
Co-reporter:Jinxia Li;Feng Zhao
Science Bulletin 2016 Volume 61( Issue 23) pp:1788-1790
Publication Date(Web):2016 December
DOI:10.1007/s11434-016-1203-y
Co-reporter:Yantao Li;Jinglong Tang;Liangcan He;Yong Liu;Yaling Liu;Zhiyong Tang
Advanced Materials 2015 Volume 27( Issue 27) pp:4075-4080
Publication Date(Web):
DOI:10.1002/adma.201501779
Co-reporter:Yingying Xu, Liming Wang, Ru Bai, Tianlu Zhang and Chunying Chen
Nanoscale 2015 vol. 7(Issue 38) pp:16100-16109
Publication Date(Web):02 Sep 2015
DOI:10.1039/C5NR04200C
Monocytes/macrophages are important constituents of the innate immune system. Monocyte–macrophage differentiation is not only crucial for innate immune responses, but is also related to some cardiovascular diseases. Silver nanoparticles (AgNPs) are one of the most widely used nanomaterials because of their broad-spectrum antimicrobial properties. However, the effect of AgNPs on the functions of blood monocytes is scarcely reported. Here, we report the impedance effect of AgNPs on THP-1 monocyte differentiation, and that this effect was mediated by autophagy blockade and lysosomal impairment. Firstly, AgNPs inhibit phorbol 12-myristate 13-acetate (PMA)-induced monocyte differentiation by down-regulating both expression of surface marker CD11b and response to lipopolysaccharide (LPS) stimulation. Secondly, autophagy is activated during PMA-induced THP-1 monocyte differentiation, and the autophagy inhibitor chloroquine (CQ) can inhibit this process. Thirdly, AgNPs block the degradation of the autophagy substrate p62 and induce autophagosome accumulation, which demonstrates the blockade of autophagic flux. Fourthly, lysosomal impairments including alkalization and decrease of lysosomal membrane stability were observed in AgNP-treated THP-1 cells. In conclusion, we demonstrate that the impedance of monocyte–macrophage differentiation by AgNPs is mediated by autophagy blockade and lysosomal dysfunction. Our results suggest that crosstalk exists in different biological effects induced by AgNPs.
Co-reporter:Kelei Hu, Huige Zhou, Ying Liu, Zhu Liu, Jing Liu, Jinglong Tang, Jiayang Li, Jiakun Zhang, Wang Sheng, Yuliang Zhao, Yan Wu and Chunying Chen
Nanoscale 2015 vol. 7(Issue 18) pp:8607-8618
Publication Date(Web):02 Apr 2015
DOI:10.1039/C5NR01084E
Cancer stem cells (CSCs) have the ability to transform into bulk cancer cells, to promote tumor growth and establish tumor metastasis. To effectively inhibit tumor growth and prevent metastasis, treatments with conventional chemotherapy drugs should be combined with CSC targeted drugs. In this study, we describe the synthesis and characterization of a new amphiphilic polymer, hyaluronic acid-cystamine-polylactic-co-glycolic acid (HA-SS-PLGA), composed of a hydrophobic PLGA head and a hydrophilic HA segment linked by a bioreducible disulfide bond. With a double emulsion method, a nano delivery system was constructed to deliver doxorubicin (DOX) and cyclopamine (CYC, a primary inhibitor of the hedgehog signaling pathway of CSCs) to both a CD44-overexpressing breast CSC subpopulation and bulk breast cancer cells and allow an on-demand release. The resulting drug-loaded NPs exhibited a redox-responsive drug release profile. Dual drug-loaded particles potently diminished the number and size of tumorspheres and HA showed a targeting effect towards breast CSCs. In vivo combination therapy further demonstrated a remarkable synergistic anti-tumor effect and prolonged survival compared to mono-therapy using the orthotopic mammary fat pad tumor growth model. The co-delivery of drug and the CSC specific inhibitor towards targeted cancer chemotherapeutics provides an insight into anticancer strategy with facile control and high efficacy.
Co-reporter:Mingjing Cao, Pengyang Wang, Yu Kou, Jing Wang, Jing Liu, Yanhui Li, Jiayang Li, Liming Wang, and Chunying Chen
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 45) pp:25014
Publication Date(Web):September 29, 2015
DOI:10.1021/acsami.5b06938
The combination of therapy and diagnosis has been emerging as a promising strategy for cancer treatment. To realize chemotherapy, photothermal therapy, and magnetic resonance imaging (MRI) in one system, we have synthesized a new magnetic nanoparticle (Gd@SiO2-DOX/ICG-PDC) integrating doxorubicin (DOX), indocyanine green (ICG), and gadolinium(III)-chelated silica nanospheres (Gd@SiO2) with a poly(diallyldimethylammonium chloride) (PDC) coating. PDC coating serves as a polymer layer to protect from quick release of drugs from the nanocarriers and increase cellular uptake. The DOX release from Gd@SiO2-DOX/ICG-PDC depends on pH and temperature. The process will be accelerated in the acidic condition than in a neutral pH 7.4. Meanwhile, upon laser irradiation, the photothermal effects promote DOX release and improve the therapeutic efficacy compared to either DOX-loaded Gd@SiO2 or ICG-loaded Gd@SiO2. Moreover, MRI results show that the Gd@SiO2-PDC nanoparticles are safe T1-type MRI contrast agents for imaging. The Gd@SiO2-PDC nanoparticles loaded with DOX and ICG can thus act as a promising theranostic platform for multimodal cancer treatment.Keywords: chemotherapy; drug delivery; gadolinium(III)-chelated silica nanospheres; magnetic resonance imaging; mesoporous silica nanoparticles; multimodal therapy; photothermal therapy
Co-reporter:Long Qin;Peng Wang;Yuanwang Guo;Minghua Liu
Advanced Science 2015 Volume 2( Issue 11) pp:
Publication Date(Web):
DOI:10.1002/advs.201500134
Co-reporter:Jing Wang, Ru Bai, Ru Yang, Jing Liu, Jinglong Tang, Ying Liu, Jiayang Li, Zhifang Chai and Chunying Chen
Metallomics 2015 vol. 7(Issue 3) pp:516-524
Publication Date(Web):28 Jan 2015
DOI:10.1039/C4MT00340C
Engineered gold nanoparticles (AuNPs) have recently drawn an increased interest in disease diagnostics and therapies. However, reports on detailed studies of AuNPs regarding their pharmacodynamics, pharmacokinetics, biodistribution, metabolism and potential toxicity are limited. It is common knowledge that the in vivo behavior and fate of various AuNPs are influenced by their surface and size. However, a comprehensive description and understanding of all variables is crucial for their further development toward potential clinical use. In this article, we describe the pharmacokinetics and biodistribution of mesoporous silica-coated gold nanorods functionalized with polyethylene glycol or bovine serum albumin (AuNR@SiO2-PEG and AuNR@SiO2-BSA, respectively) in tumor-bearing balb/c mice. To gain further insight into the pharmacokinetics, biodistribution and tumor uptake, we also compare the results with BSA functionalized gold nanorods (AuNR-BSA) and gold clusters (AuNC-BSA). The results reveal that AuNR@SiO2-PEG have the longest blood half-life and the maximum percentage content in the tumor at 24 h and 3 days compared to other AuNPs. AuNR@SiO2-PEG, AuNR@SiO2-BSA and AuNR-BSA had primarily accumulated in the liver and spleen without apparent metabolism after 3 days, while the content of AuNC-BSA in the liver, spleen and kidneys showed an obvious decrease, indicating a size-dependent metabolism process. Our results demonstrate how to manipulate the size and surface chemistry of AuNPs to prolong their blood circulation time, improve delivery into target organs and achieve a safer design of nanomedicines.
Co-reporter:Jing Wang, Yadian Xie, Liming Wang, Jinglong Tang, Jiayang Li, Duygu Kocaefe, Yasar Kocaefe, Zhiwen Zhang, Yaping Li and Chunying Chen
RSC Advances 2015 vol. 5(Issue 10) pp:7529-7538
Publication Date(Web):22 Dec 2014
DOI:10.1039/C4RA13228A
Metallic nanomaterials, especially gold nanoparticles, which have low toxicity and high photothermal conversion efficiency, exhibit promising theranostic applications in biomedical fields. However, detailed preclinical studies of these nanomaterials, such as pharmacokinetics, metabolism, long-term stability and toxicity potential should still be performed. Photoacoustic imaging as a novel non-invasive imaging technique provides convenience for studying real-time semiquantitative pharmacokinetic and biodistribution profiles of drugs or probes to determine whether they can reach the target areas and their metabolic pathways. In this article, we prepared chitosan-capped star shaped gold nanoparticles (AuNSs) and used multispectral optoacoustic tomography (MSOT) to visualize AuNSs in the blood vessels, liver, spleen and kidneys in real time. We also compared these results with chitosan-capped rod shaped gold nanoparticles (AuNRs). The results show that both AuNSs and AuNRs experience rapid blood clearance and have fast and long-term accumulation in the liver and spleen (reaching the peak value within 10 min). The pharmacokinetic data of the two gold nanoparticles fitted to the two-compartment model. The important pharmacokinetic parameters were calculated. The results from MSOT were qualitatively validated by inductively coupled plasma mass spectrometery (ICP-MS). Our results demonstrate that MSOT can serve as an effective tool to monitor gold nanoparticles' pharmacokinetics and biodistribution in specific organs.
Co-reporter:Rui Chen, Lili Zhang, Cuicui Ge, Michael T. Tseng, Ru Bai, Ying Qu, Christiane Beer, Herman Autrup, and Chunying Chen
Chemical Research in Toxicology 2015 Volume 28(Issue 3) pp:440
Publication Date(Web):January 12, 2015
DOI:10.1021/tx5004003
The tremendous demand of the market for carbon nanotubes has led to their massive production that presents an increasing risk through occupational exposure. Lung deposition of carbon nanotubes is known to cause acute localized pulmonary adverse effects. However, systemic cardiovascular damages associated with acute pulmonary lesion have not been thoroughly addressed. Four kinds of multiwalled carbon nanotubes (MWCNTs) with different lengths and/or iron contents were used to explore the potential subchronic toxicological effects in spontaneously hypertensive (SH) rats and normotensive control Wistar-Kyoto (WKY) rats after intratracheal instillation. MWCNTs penetrated the lung blood–gas barrier and accumulated in the liver, kidneys, and spleen but not in the heart and aorta of SH rats. The pulmonary toxicity and cardiovascular effects were assessed at 7 and 30 days postexposure. Compared to the WKY rats, transient influences on blood pressure and up to 30 days persistent decrease in the heart rate of SH rats were found by electrocardiogram monitoring. The subchronic toxicity, especially the sustained inflammation of the pulmonary and cardiovascular system, was revealed at days 7 and 30 in both SH and WKY rat models. Histopathological results showed obvious morphological lesions in abdominal arteries of SH rats 30 days after exposure. Our results suggest that more attention should be paid to the long-term toxic effects of MWCNTs, and particularly, occupationally exposed workers with preexisting cardiovascular diseases should be monitored more thoroughly.
Co-reporter:Jing Liu, Xiaopeng Zheng, Liang Yan, Liangjun Zhou, Gan Tian, Wenyan Yin, Liming Wang, Ying Liu, Zhongbo Hu, Zhanjun Gu, Chunying Chen, and Yuliang Zhao
ACS Nano 2015 Volume 9(Issue 1) pp:696
Publication Date(Web):January 5, 2015
DOI:10.1021/nn506137n
Here, we present a precision cancer nanomedicine based on Bi2S3 nanorods (NRs) designed specifically for multispectral optoacoustic tomography (MSOT)/X-ray computed tomography (CT)-guided photothermal therapy (PTT). The as-prepared Bi2S3 NRs possess ideal photothermal effect and contrast enhancement in MSOT/CT bimodal imaging. These features make them simultaneously act as “satellite” and “precision targeted weapon” for the visual guide to destruction of tumors in vivo, realizing effective tumor destruction and metastasis inhibition after intravenous injection. In addition, toxicity screening confirms that Bi2S3 NRs have well biocompatibility. This triple-modality-nanoparticle approach enables simultaneously precise cancer therapy and therapeutic monitoring.Keywords: Bi2S3 nanorods; multispectral optoacoustic tomography; photothermal therapy; thin bandgap semiconductor; X-ray computed tomography;
Co-reporter:Liming Wang, Tianlu Zhang, Panyun Li, Wanxia Huang, Jinglong Tang, Pengyang Wang, Jing Liu, Qingxi Yuan, Ru Bai, Bai Li, Kai Zhang, Yuliang Zhao, and Chunying Chen
ACS Nano 2015 Volume 9(Issue 6) pp:6532
Publication Date(Web):May 20, 2015
DOI:10.1021/acsnano.5b02483
To predict potential medical value or toxicity of nanoparticles (NPs), it is necessary to understand the chemical transformation during intracellular processes of NPs. However, it is a grand challenge to capture a high-resolution image of metallic NPs in a single cell and the chemical information on intracellular NPs. Here, by integrating synchrotron radiation-beam transmission X-ray microscopy (SR-TXM) and SR-X-ray absorption near edge structure (SR-XANES) spectroscopy, we successfully capture the 3D distribution of silver NPs (AgNPs) inside a single human monocyte (THP-1), associated with the chemical transformation of silver. The results reveal that the cytotoxicity of AgNPs is largely due to the chemical transformation of particulate silver from elemental silver (Ag0)n, to Ag+ ions and Ag–O–, then Ag–S– species. These results provide direct evidence in the long-lasting debate on whether the nanoscale or the ionic form dominates the cytotoxicity of silver nanoparticles. Further, the present approach provides an integrated strategy capable of exploring the chemical origins of cytotoxicity in metallic nanoparticles.Keywords: AgNPs; chemical origin; chemical transformation; dynamic processes of intracellular nanoparticles; nano-CT; nanotoxicity;
Co-reporter:Rui Chen, Daishun Ling, Lin Zhao, Shuaifei Wang, Ying Liu, Ru Bai, Seungmin Baik, Yuliang Zhao, Chunying Chen, and Taeghwan Hyeon
ACS Nano 2015 Volume 9(Issue 12) pp:12425
Publication Date(Web):November 15, 2015
DOI:10.1021/acsnano.5b05783
Magnetic resonance imaging (MRI) contrast agents with high relaxivity are highly desirable because they can significantly increase the accuracy of diagnosis. However, they can be potentially toxic to the patients. In this study, using a mouse model, we investigate the toxic effects and subsequent tissue damage induced by three T1 MRI contrast agents: gadopentetate dimeglumine injection (GDI), a clinically used gadolinium (Gd)-based contrast agent (GBCAs), and oxide nanoparticle (NP)-based contrast agents, extremely small-sized iron oxide NPs (ESIONs) and manganese oxide (MnO) NPs. Biodistribution, hematological and histopathological changes, inflammation, and the endoplasmic reticulum (ER) stress responses are evaluated for 24 h after intravenous injection. These thorough assessments of the toxic and stress responses of these agents provide a panoramic description of safety concerns and underlying mechanisms of the toxicity of contrast agents in the body. We demonstrate that ESIONs exhibit fewer adverse effects than the MnO NPs and the clinically used GDI GBCAs, providing useful information on future applications of ESIONs as potentially safe MRI contrast agents.Keywords: biodistribution; contrast agent; endoplasmic reticulum stress; iron oxide nanoparticles; magnetic resonance imaging; toxicity evaluation;
Co-reporter:Yu-Feng Li, Jiating Zhao, Ying Qu, Yuxi Gao, Zhenghang Guo, Zuoliang Liu, Yuliang Zhao, Chunying Chen
Nanomedicine: Nanotechnology, Biology and Medicine 2015 Volume 11(Issue 6) pp:1531-1549
Publication Date(Web):August 2015
DOI:10.1016/j.nano.2015.04.008
Nanotoxicology studies the interactions of engineered nanomaterials with biological systems. Traditional in vitro and in vivo toxicological assays have been successfully employed. However, the toxicological mechanisms of nanoparticles might not be the same as those incurred in traditional molecular toxicology. Furthermore, how to realize in situ and real time measurements especially in the biological microenvironment is still a challenge. Synchrotron radiation, which is highly polarized and tunable, has been proved to play an indispensible role for nanotoxicology studies. In this review, the role of synchrotron radiation techniques is summarized in screening physicochemical characteristics, in vitro and in vivo behaviors, and ecotoxicological effects of engineered nanomaterials.From the Clinical EditorThe rapid gain in popularity of nanomaterials has also raised the concern of nanotoxicity, which needs to be assessed and addressed. In this comprehensive review, the authors outlined the underlying principles of using synchrotron radiation techniques for nanotoxicology studies and also in other scientific fields.In this review, the application of synchrotron radiation techniques is summarized in screening the physicochemical characteristics, in vitro and in vivo behaviors, and ecotoxicological effects of engineered nanomaterials.
Co-reporter:Chunying Chen
Science Bulletin 2015 Volume 60( Issue 20) pp:1787-1788
Publication Date(Web):2015 October
DOI:10.1007/s11434-015-0909-6
Co-reporter:Wenshu Cong, Peng Wang, Ying Qu, Jinglong Tang, Ru Bai, Yuliang Zhao, Chunying Chen, Xiaolin Bi
Biomaterials 2015 42() pp: 78-86
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.11.048
Co-reporter:Lingling Huo, Rui Chen, Lin Zhao, Xiaofei Shi, Ru Bai, Dingxin Long, Feng Chen, Yuliang Zhao, Yan-Zhong Chang, Chunying Chen
Biomaterials 2015 61() pp: 307-315
Publication Date(Web):
DOI:10.1016/j.biomaterials.2015.05.029
Co-reporter:Zhenjiang Zhang ; Jing Wang ; Xin Nie ; Tao Wen ; Yinglu Ji ; Xiaochun Wu ; Yuliang Zhao
Journal of the American Chemical Society 2014 Volume 136(Issue 20) pp:7317-7326
Publication Date(Web):April 28, 2014
DOI:10.1021/ja412735p
External stimuli, such as ultrasound, magnetic field, and light, can be applied to activate in vivo tumor targeting. Herein, we fabricated polymer encapsulated gold nanorods to couple the photothermal properties of gold nanorods and the thermo- and pH-responsive properties of polymers in a single nanocomposite. The activation mechamism was thus transformed from heat to near-infrared (NIR) laser, which can be more easily controlled. Doxorubicin, a clinical anticancer drug, can be loaded into the nanocomposite through electrostatic interactions with high loading content up to 24%. The nanocomposite’s accumulation in tumor post systematic administration can be significantly enhanced by NIR laser irradiation, providing a prerequisite for their therapeutic application which almost completely inhibited tumor growth and lung metastasis. Since laser can be manipulated very precisely and flexibly, the nanocomposite provides an ideally versatile platform to simultaneously deliver heat and anticancer drugs in a laser-activation mechanism with facile control of the area, time, and dosage. The NIR laser-induced targeted cancer thermo-chemotherapy without using targeting ligands represents a novel targeted anticancer strategy with facile control and practical efficacy.
Co-reporter:Liming Wang;Xiaoying Lin;Jing Wang;Zhijian Hu;Yinglu Ji;Shuai Hou;Yuliang Zhao;Xiaochun Wu
Advanced Functional Materials 2014 Volume 24( Issue 27) pp:4229-4239
Publication Date(Web):
DOI:10.1002/adfm.201400015
Chemotherapy resistance remains a large obstacle to successful clinical cancer therapy, mainly due to little accumulation and low sensitivity of drugs and the effective clinical strategy still lacks. Herein, a novel yet simple strategy to combat cancer drug resistance using the plasmonic feature-based photothermal properties is reported. Rather than directly killing cancer cells using nanoparticle-mediated hyperthermia, for the first time, localized plasmonic heating of gold nanorod at a mild laser power density can modulate the drug-resistance related genes. This photothermal effect triggers higher expression of heat shock factor (HSF-1) trimers and depresses the expression of P-glycoprotein (Pgp) and mutant p53. In turn, both drug accumulation in the breast cancer resistant cells (MCF-7/ADR) and their sensitiveness to drugs can be greatly enhanced. Considering the universality and feasibility of this strategy, it points out a new unique way to challenge drug resistance.
Co-reporter:Teng Zhou;Meifang Yu;Bo Zhang;Liming Wang;Xiaochun Wu;Hejiang Zhou;Yipeng Du;Junfeng Hao;Yaping Tu;Taotao Wei
Advanced Functional Materials 2014 Volume 24( Issue 44) pp:6922-6932
Publication Date(Web):
DOI:10.1002/adfm.201401642
Gold nanorods have received much attention because of their distinct physicochemical properties and promising applications in bioimaging, biosensing, drug delivery, photothermal therapy, and optoelectronic devices. However, little is known regarding their effect on tumor metastasis. In the present investigation, serum protein-coated gold nanorods (AuNRs) at low concentrations is shown to exhibit no apparent effects on the viability and proliferation of three different metastatic cancer cell lines, that is, MDA-MB-231 human breast cancer cells, PC3 human prostate cancer cells, and B16F10 mouse melanoma cells, but effectively inhibit their migration and invasion in vitro. Quantitative proteomics and real-time PCR array analyses indicate that exposure of cells to AuNRs can down-regulate the expression of diverse energy generation-related genes, which accounts for their inhibition of mitochondrial oxidative phosphorylation (OXPHOS) and glycolysis. The impairment of OXPHOS and glycolysis results in a distinctive reduction of ATP production and subsequent inhibition of F-actin cytoskeletal assembly, which is crucial for the migration and invasion of cancer cells. The inhibitory effect of AuNRs on cancer cell migration is also confirmed in vivo. Taken together, the unique mechanism in inhibiting cancer cell migration by AuNRs might provide a new approach to specific cancer therapeutic treatment.
Co-reporter:Xin Nie, Jiakun Zhang, Qing Xu, Xiaoguang Liu, Yaping Li, Yan Wu and Chunying Chen
Journal of Materials Chemistry A 2014 vol. 2(Issue 21) pp:3232-3242
Publication Date(Web):03 Mar 2014
DOI:10.1039/C3TB21744B
In this paper, we report a novel targeting drug delivery system, obtained using an amphiphilic chitosan-co-(D,L-lactide)/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer (CS-co-PLA/DPPE) with the modification of an iRGD (CRGDKGPDC) peptide as the targeting module. Hydrophilic doxorubicin (DOX) was encapsulated and cell experiments were carried out to evaluate the anti-tumor efficacy of DOX-loaded nanoparticles (NPs) in vitro. Characterization data showed a favorable size distribution, high encapsulation efficiency and a pH-dependent release profile for the synthesized NPs. A cytotoxicity assay revealed the higher inhibitory effect of DOX–iRGD–NPs especially in cell lines with an abundant expression of αvβ3 integrin receptors. An increased cellular uptake of DOX–iRGD–NPs was observed and further confirmed to be a consequence of a specific endocytosis pathway mediated by ligand–receptor interactions. Visualization of the intracellular trafficking showed different distributions of DOX when delivered using DOX–NPs and DOX–iRGD–NPs, proving the targeting effect of iRGD. With the help of the iRGD targeting peptide, a chemotherapeutic drug can be delivered specifically to the cancer and endothelial cells expressing αvβ3 integrin receptors to achieve an enhanced anti-tumor efficacy and controlled drug release.
Co-reporter:Jinglong Tang, Xiumei Jiang, Liming Wang, Hui Zhang, Zhijian Hu, Ying Liu, Xiaochun Wu and Chunying Chen
Nanoscale 2014 vol. 6(Issue 7) pp:3670-3678
Publication Date(Web):25 Feb 2014
DOI:10.1039/C3NR06841B
Due to aspect ratio dependent localized surface plasmon resonance (SPR), gold nanorods (Au NRs) can be tuned to have a strong absorption in the near infrared region (NIR) and convert light to heat energy, which shows promises in cancer photothermal therapy. In this study, we introduced another more efficient NIR photothermal agent, Au nanorods coated with a shell of Pt nanodots (Au@Pt nanostructures). After surface modification with Pt dots, the Au@Pt nanostructure became a more efficient photothermal therapy agent as verified both in vitro and in vivo. To clarify the mechanism, we assessed the interaction between the MDA-MB-231 cells with Au@Pt or Au NRs. Results showed that the slightly higher uptake and the reduced sensitivity of the longitudinal SPR band on the intracellular aggregate state may contribute to the better photothermal efficiency for Au@Pt NRs. The theoretical studies further confirmed that the Au@Pt nanostructure itself exhibited better photothermal efficiency compared to Au NRs. These advantages make the Au@Pt nanostructure a more attractive and effective agent for cancer photothermal therapy than general Au NRs.
Co-reporter:Yu-Feng Li, Yuxi Gao, Zhifang Chai and Chunying Chen
Metallomics 2014 vol. 6(Issue 2) pp:220-232
Publication Date(Web):13 Jan 2014
DOI:10.1039/C3MT00316G
Metallomics, focusing on the global and systematic understanding of the metal uptake, trafficking, role and excretion in biological systems, has attracted more and more attention. Metal-related nanomaterials, including metallic and metal-containing nanomaterials, have unique properties compared to their micro-scaled counterparts and therefore require special attention. The small size effect, surface effect, and quantum size effect directly influence the physicochemical properties of nanostructured materials and their fate and behavior in biota. However, to our knowledge, the metallomics itself did not touch this special category of materials yet. Therefore, the term “nanometallomics” is proposed and the systematic study on the absorption, distribution, metabolism, excretion (ADME) behavior of metal-related nanomaterials in biological systems and their interactions with genes, proteins and other biomolecules will be reviewed. The ADME behavior of metal-related nanomaterials in the biological systems is influenced by their physicochemical properties, the exposure route, and the microenvironment of the deposition site. Nanomaterials may not only interact directly or indirectly with genes, proteins and other molecules to cause DNA damage, genotoxicity, immunotoxicity, and cytotoxicity, but also stimulate the immune responses, circumvent tumor resistance and inhibit tumor metastasis. Nanometallomics needs to be integrated with other omics sciences, such as genomics, proteomics and metabolomics, to explore the biomedical data and obtain the overall knowledge of underlying mechanisms, and therefore to improve the application performance and to reduce the potential risk of metal-related nanomaterials.
Co-reporter:Rui Chen, Lingling Huo, Xiaofei Shi, Ru Bai, Zhenjiang Zhang, Yuliang Zhao, Yanzhong Chang, and Chunying Chen
ACS Nano 2014 Volume 8(Issue 3) pp:2562
Publication Date(Web):February 3, 2014
DOI:10.1021/nn406184r
Zinc oxide nanoparticles (ZnO NPs) have been widely used in cosmetics and sunscreens, advanced textiles, self-charging and electronic devices; the potential for human exposure and the health impact at each stage of their manufacture and use are attracting great concerns. In addition to pulmonary damage, nanoparticle exposure is also strongly correlated with the increase in incidences of cardiovascular diseases; however, their toxic potential remains largely unclear. Herein, we investigated the cellular responses and endoplasmatic reticulum (ER) stress induced by ZnO NPs in human umbilical vein endothelial cells (HUVECs) in comparison with the Zn2+ ions and CeO2 NPs. We found that the dissolved zinc ion was the most significant factor for cytotoxicity in HUVECs. More importantly, ZnO NPs at noncytotoxic concentration, but not CeO2 NPs, can induce significant cellular ER stress response with higher expression of spliced xbp-1, chop, and caspase-12 at the mRNA level, and associated ER marker proteins including BiP, Chop, GADD34, p-PERK, p-eIF2α, and cleaved Caspase-12 at the protein levels. Moreover, ER stress was widely activated after treatment with ZnO NPs, while six of 84 marker genes significantly increased. ER stress response is a sensitive marker for checking the interruption of ER homeostasis by ZnO NPs. Furthermore, higher dosage of ZnO NPs (240 μM) quickly rendered ER stress response before inducing apoptosis. These results demonstrate that ZnO NPs activate ER stress-responsive pathway and the ER stress response might be used as an earlier and sensitive end point for nanotoxicological study.Keywords: apoptosis; ceria; cytotoxicity; ER stress; nanoparticles; signaling pathways; ZnO
Co-reporter:Hejiang Zhou, Bo Zhang, Jiajia Zheng, Meifang Yu, Teng Zhou, Kai Zhao, Yanxia Jia, Xingfa Gao, Chunying Chen, Taotao Wei
Biomaterials 2014 35(5) pp: 1597-1607
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.11.020
Co-reporter:Shuai Xu, Jing Liu, Dian Li, Liming Wang, Jia Guo, Changchun Wang, Chunying Chen
Biomaterials 2014 35(5) pp: 1676-1685
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.10.081
Co-reporter:Xiaonan Lv, Peng Wang, Ru Bai, Yingying Cong, Siqingaowa Suo, Xiaofeng Ren, Chunying Chen
Biomaterials 2014 35(13) pp: 4195-4203
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.01.054
Co-reporter:Yingying Xu, Jing Wang, Xiaofan Li, Ying Liu, Luru Dai, Xiaochun Wu, Chunying Chen
Biomaterials 2014 35(16) pp: 4667-4677
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.02.035
Co-reporter:Ying Liu, Yuliang Zhao, Baoyun Sun, and Chunying Chen
Accounts of Chemical Research 2013 Volume 46(Issue 3) pp:702
Publication Date(Web):September 21, 2012
DOI:10.1021/ar300028m
Because of their unique physical, chemical, electrical, and mechanical properties, carbon nanotubes (CNTs) have attracted a great deal of research interest and have many potential applications. As large-scale production and application of CNTs increases, the general population is more likely to be exposed to CNTs either directly or indirectly, which has prompted considerable attention about human health and safety issues related to CNTs. Although considerable experimental data related to CNT toxicity at the molecular, cellular, and whole animal levels have been published, the results are often conflicting. Therefore, a systematic understanding of CNT toxicity is needed but has not yet been developed.In this Account, we highlight recent investigations into the basis of CNT toxicity carried out by our team and by other laboratories. We focus on several important factors that explain the disparities in the experimental results of nanotoxicity, such as impurities, amorphous carbon, surface charge, shape, length, agglomeration, and layer numbers. The exposure routes, including inhalation, intravenous injection, or dermal or oral exposure, can also influence the in vivo behavior and fate of CNTs. The underlying mechanisms of CNT toxicity include oxidative stress, inflammatory responses, malignant transformation, DNA damage and mutation (errors in chromosome number as well as disruption of the mitotic spindle), the formation of granulomas, and interstitial fibrosis. These findings provide useful insights for de novo design and safe application of carbon nanotubes and their risk assessment to human health.To obtain reproducible and accurate results, researchers must establish standards and reliable detection methods, use standard CNT samples as a reference control, and study the impact of various factors systematically. In addition, researchers need to examine multiple types of CNTs, different cell lines and animal species, multidimensional evaluation methods, and exposure conditions. To make results comparable among different institutions and countries, researchers need to standardize choices in toxicity testing such as that of cell line, animal species, and exposure conditions. The knowledge presented here should lead to a better understanding of the key factors that can influence CNT toxicity so that their unwanted toxicity might be avoided.
Co-reporter:Zhenjiang Zhang;Jing Wang
Advanced Materials 2013 Volume 25( Issue 28) pp:3869-3880
Publication Date(Web):
DOI:10.1002/adma.201301890
Abstract
While thermo-chemotherapy has proved to be effective in optimizing the efficacies of cancer treatments, traditional chemotherapy is subject to adverse side effects and heat delivery is often challenging in operation. Some photothermal inorganic nanoparticles responsive to near infrared light provide new opportunities for simultaneous and targeted delivery of heat and chemotherapeutics to the tumor sites in pursuit of synergistic effects for efficacy enhancement. The state of the art of nanoparticle-induced thermo-chemotherapy is summarized and the advantages and challenges of the major nanoplatforms based on gold nanoparticles, carbon nanomaterials, palladium nanosheets, and copper-based nanocrystals are highlighted. In addition, the optical-imaging potentials of the nanoplatforms that may endow them with imaging-guided therapy and therapeutic-result-monitoring capabilities are also briefly discussed.
Co-reporter:Ligeng Xu;Ye Liu;Zhiyun Chen;Wei Li;Ying Liu;Liming Wang;Liying Ma;Yiming Shao;Yuliang Zhao
Advanced Materials 2013 Volume 25( Issue 41) pp:5928-5936
Publication Date(Web):
DOI:10.1002/adma.201300583
Co-reporter:Liming Wang ; Jingyuan Li ; Jun Pan ; Xiumei Jiang ; Yinglu Ji ; Yufeng Li ; Ying Qu ; Yuliang Zhao ; Xiaochun Wu
Journal of the American Chemical Society 2013 Volume 135(Issue 46) pp:17359-17368
Publication Date(Web):November 12, 2013
DOI:10.1021/ja406924v
Regarding the importance of the biological effects of nanomaterials, there is still limited knowledge about the binding structure and stability of the protein corona on nanomaterials and the subsequent impacts. Here we designed a hard serum albumin protein corona (BSA) on CTAB-coated gold nanorods (AuNRs) and captured the structure of protein adsorption using synchrotron radiation X-ray absorption spectroscopy, microbeam X-ray fluorescent spectroscopy, and circular dichroism in combination with molecular dynamics simulations. The protein adsorption is attributed to at least 12 Au–S bonds and the stable corona reduced the cytotoxicity of CTAB/AuNRs. These combined strategies using physical, chemical, and biological approaches will improve our understanding of the protective effects of protein coronas against the toxicity of nanomaterials. These findings have shed light on a new strategy for studying interactions between proteins and nanomaterials, and this information will help further guide the rational design of nanomaterials for safe and effective biomedical applications.
Co-reporter:Liming Wang, Xiumei Jiang, Yinglu Ji, Ru Bai, Yuliang Zhao, Xiaochun Wu and Chunying Chen
Nanoscale 2013 vol. 5(Issue 18) pp:8384-8391
Publication Date(Web):22 Jul 2013
DOI:10.1039/C3NR01626A
We investigated how surface chemistry influences the interaction between gold nanorods (AuNRs) and cell membranes and the subsequent cytotoxicity arising from them in a serum-free cell culture system. Our results showed that the AuNRs coated with cetyl trimethylammonium bromide (CTAB) molecules can generate defects in the cell membrane and induce cell death, mainly due to the unique bilayer structure of CTAB molecules on the surface of the rods rather than their charge. Compared to CTAB-capped nanorods, positively charged polyelectrolyte-coated, i.e. poly(diallyldimethyl ammonium chloride) (PDDAC), AuNRs show improved biocompatibility towards cells. Thus, the present results indicate that the nature of surface molecules, especially their packing structures on the surface of AuNRs rather than surface charge, play a more crucial role in determining cytotoxicity. These findings about interfacial interactions could also explain the effects of internalized AuNRs on the structures or functions of organelles. This study will help understanding of the toxic nature of AuNRs and guide rational design of the surface chemistry of AuNRs for good biocompatibility in pharmaceutical therapy.
Co-reporter:Limin Zhang, Liming Wang, Yili Hu, Zhigang Liu, Yuan Tian, Xiaochun Wu, Yuliang Zhao, Huiru Tang, Chunying Chen, Yulan Wang
Biomaterials 2013 34(29) pp: 7117-7126
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.05.043
Co-reporter:Jiakun Zhang;Min Li;Tengfei Fan;Qing Xu;Yan Wu
Journal of Polymer Research 2013 Volume 20( Issue 3) pp:
Publication Date(Web):2013 March
DOI:10.1007/s10965-013-0107-7
Nanoparticles of a novel amphiphilic copolymer of chitosan with poly(lactide) (PLA) and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) were generated. The chemical structure of the copolymer was determined using Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance spectroscopy (NMR), and thermogravimetric analysis (TGA). Nanoprecipitation or emulsion/solvent evaporation was employed to prepare nanoparticles of this copolymer loaded with a lipophilic organophosphorus pesticide, chlorpyrifos. The nanoparticle size was adjusted to between 100 and 300 nm by varying the copolymer/chlorpyrifos mass ratio in the two nanoparticle preparation methods. The resulting nanoparticles exhibited high chlorpyrifos loading capacity (LC) and sustained release profiles. The nanoparticle size, loading content (LC), and encapsulation efficiency (EE) decreased with increasing mass ratio of copolymer to chlorpyrifos. Chlorpyrifos release was controlled by adjusting the ratio of copolymer to chlorpyrifos. The study showed that these chitosan-co-PLA-DPPE copolymer nanoparticles can be used as carriers for lipophilic pesticide delivery.
Co-reporter:Ligeng Xu, Ye Liu, Zhiyun Chen, Wei Li, Ying Liu, Liming Wang, Yong Liu, Xiaochun Wu, Yinglu Ji, Yuliang Zhao, Liying Ma, Yiming Shao, and Chunying Chen
Nano Letters 2012 Volume 12(Issue 4) pp:2003-2012
Publication Date(Web):February 28, 2012
DOI:10.1021/nl300027p
With the intense international response to the AIDS pandemic, HIV vaccines have been extensively investigated but have failed due to issues of safety or efficacy in humans. Adjuvants for HIV/AIDS vaccines are under intense research but a rational design approach is still lacking. Nanomaterials represent an obvious opportunity in this field due to their unique physicochemical properties. Gold nanostructures are being actively studied as a promising and versatile platform for biomedical application. Herein, we report novel surface-engineered gold nanorods (NRs) used as promising DNA vaccine adjuvant for HIV treatment. We have exploited the effects of surface chemistry on the adjuvant activity of the gold nanorod by placing three kinds of molecules, that is, cetyltrimethylammonium bromide (CTAB), poly(diallydimethylammonium chloride) (PDDAC), and polyethyleneimine (PEI) on the surface of the nanorod. These PDDAC- or PEI-modified Au NRs can significantly promote cellular and humoral immunity as well as T cell proliferation through activating antigen-presenting cells if compared to naked HIV-1 Env plasmid DNA treatment in vivo. These findings have shed light on the rational design of low-toxic nanomaterials as a versatile platform for vaccine nanoadjuvants/delivery systems.
Co-reporter:Cuicui Ge, Yang Li, Jun-Jie Yin, Ying Liu, Liming Wang, Yuliang Zhao and Chunying Chen
NPG Asia Materials 2012 4(12) pp:e32
Publication Date(Web):2012-12-01
DOI:10.1038/am.2012.60
Due to the existence of considerable quantities of metallic and carbonaceous impurities, the key factor and mechanism for the reported toxicity of carbon nanotubes (CNTs) are unclear. Here, we first quantify the contribution of metal residues and fiber structure to the toxicity of CNTs. Significant quantities of metal particles could be mobilized from CNTs into surrounding fluids, depending on the properties and constituents of the biological microenvironment, as well as the properties of metal particles. Furthermore, electron spin resonance measurements confirm that hydroxyl radicals can be generated by both CNTs containing metal impurities and acid-leachable metals from CNTs. Several biomolecules facilitate the generation of free radicals, which might be due to the participation of these biomolecules in redox cycling influenced by pH. Among several major metal residues, Fe has a critical role in generating hydroxyl radicals, reducing cell viability and promoting intracellular reactive oxidative species. Cell viability is highly dependent on the amount of metal residues and iron in particular, but not tube structure, while the negative effect of CNTs themselves on cell viability is very limited in a certain concentration range below 80 μg ml−1. It is crucial to systematically understand how these exogenous and endogenous factors influence the toxicity of CNTs to avoid their undesirable toxicity.
Co-reporter:Yu-Feng Li, Zeqin Dong, Chunying Chen, Bai Li, Yuxi Gao, Liya Qu, Tianchen Wang, Xin Fu, Yuliang Zhao, and Zhifang Chai
Environmental Science & Technology 2012 Volume 46(Issue 20) pp:11313-11318
Publication Date(Web):October 3, 2012
DOI:10.1021/es302241v
Due to a long history of extensive mercury mining and smelting activities, local residents in Wanshan, China, are suffering from elevated mercury exposure. The objective of the present study was to study the effects of oral supplementation with selenium-enriched yeast in these long-term mercury-exposed populations. One hundred and three volunteers from Wanshan area were recruited and 53 of them were supplemented with 100 μg of organic selenium daily as selenium-enriched yeast while 50 of them were supplemented with the nonselenium-enriched yeast for 3 months. The effects of selenium supplementation on urinary mercury, selenium, and oxidative stress-related biomarkers including malondialdehyde and 8-hydroxy-2-deoxyguanosine were assessed. This 3-month selenium supplementation trial indicated that organic selenium supplementation could increase mercury excretion and decrease urinary malondialdehyde and 8-hydroxy-2-deoxyguanosine levels in local residents.
Co-reporter:Yang Li, Ying Liu, Yujian Fu, Taotao Wei, Laurent Le Guyader, Ge Gao, Ru-Shi Liu, Yan-Zhong Chang, Chunying Chen
Biomaterials 2012 33(2) pp: 402-411
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.09.091
Co-reporter:Xiu-Mei Jiang;Li-Ming Wang;Jing Wang
Applied Biochemistry and Biotechnology 2012 Volume 166( Issue 6) pp:1533-1551
Publication Date(Web):2012 March
DOI:10.1007/s12010-012-9548-4
Gold nanomaterials (Au NMs) have attracted increasing attention in biomedicine due to their facile preparation, multifunctional modifications, unique optical and electrical properties, and good biocompatibility. The physicochemical properties of Au NMs at nanoscale, like size, shape, surface chemistry, and near field effects, are rendering Au NMs potent candidates in biomedicine. Thus, risk assessment of negative effects of Au NMs on biological systems is becoming urgent and necessary for future applications. In this review, we summarize up-to-date progresses on the preparation and modification of Au NMs and their biomedical applications, including biosensor, bioimaging and phototherapy, gene/drug delivery. Finally, we discuss the potential risk of Au NMs to biological systems, which is instructive for rationally designing and preparing nanomaterials for safe applications in nanomedicine.
Co-reporter:Xin Nie
Science China Life Sciences 2012 Volume 55( Issue 10) pp:872-883
Publication Date(Web):2012 October
DOI:10.1007/s11427-012-4389-5
Au nanoparticles have been used in biomedical applications since ancient times. However, the rapid development of nanotechnology over the past century has led to recognition of the great potential of Au nanoparticles in a wide range of applications. Advanced fabrication techniques allow us to synthesize a variety of Au nanostructures possessing physiochemical properties that can be exploited for different purposes. Functionalization of the surface of Au nanoparticles further eases their application in various roles. These advantages of Au nanoparticles make them particularly suited for cancer treatment and diagnosis. The small size of Au particles enables them to preferentially accumulate at tumor sites to achieve in vivo targeting after systemic administration. Efficient light absorption followed by rapid heat conversion makes them very promising in photothermal therapy. The facile surface chemistry of Au nanoparticles eases delivery of drugs, ligands or imaging contrast agents in vivo. In this review, we summarize recent development of Au nanoparticles in cancer theranostics including imaging-based detection, photothermal therapy, chemical therapy and drug delivery. The multifunctional nature of Au nanoparticles means they hold great promise as novel anti-cancer therapeutics.
Co-reporter:Seung-gu Kang;Ying Liu;Baoyun Sun;Lina Zhao;Yuliang Zhao;Tien Huynh;Ping Yang;Huan Meng;Gengmei Xing;Guoqiang Zhou;Ruhong Zhou
PNAS 2012 Volume 109 (Issue 38 ) pp:15431-15436
Publication Date(Web):2012-09-18
DOI:10.1073/pnas.1204600109
Pancreatic adenocarcinoma is the most lethal of the solid tumors and the fourth-leading cause of cancer-related death in North
America. Matrix metalloproteinases (MMPs) have long been targeted as a potential anticancer therapy because of their seminal
role in angiogenesis and extracellular matrix (ECM) degradation of tumor survival and invasion. However, the inhibition specificity
to MMPs and the molecular-level understanding of the inhibition mechanism remain largely unresolved. Here, we found that endohedral
metallofullerenol Gd@C82(OH)22 can successfully inhibit the neoplastic activity with experiments at animal, tissue, and cellular levels. Gd@C82(OH)22 effectively blocks tumor growth in human pancreatic cancer xenografts in a nude mouse model. Enzyme activity assays also
show Gd@C82(OH)22 not only suppresses the expression of MMPs but also significantly reduces their activities. We then applied large-scale molecular-dynamics
simulations to illustrate the molecular mechanism by studying the Gd@C82(OH)22–MMP-9 interactions in atomic detail. Our data demonstrated that Gd@C82(OH)22 inhibits MMP-9 mainly via an exocite interaction, whereas the well-known zinc catalytic site only plays a minimal role. Steered
by nonspecific electrostatic, hydrophobic, and specific hydrogen-bonding interactions, Gd@C82(OH)22 exhibits specific binding modes near the ligand-specificity loop S1′, thereby inhibiting MMP-9 activity. Both the suppression
of MMP expression and specific binding mode make Gd@C82(OH)22 a potentially more effective nanomedicine for pancreatic cancer than traditional medicines, which usually target the proteolytic
sites directly but fail in selective inhibition. Our findings provide insights for de novo design of nanomedicines for fatal
diseases such as pancreatic cancer.
Co-reporter:Qing Xu, Yuexian Liu, Shishuai Su, Wei Li, Chunying Chen, Yan Wu
Biomaterials 2012 33(5) pp: 1627-1639
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.11.012
Co-reporter:Liming Wang, Ying Liu, Wei Li, Xiumei Jiang, Yinglu Ji, Xiaochun Wu, Ligeng Xu, Yang Qiu, Kai Zhao, Taotao Wei, Yufeng Li, Yuliang Zhao, and Chunying Chen
Nano Letters 2011 Volume 11(Issue 2) pp:772-780
Publication Date(Web):December 27, 2010
DOI:10.1021/nl103992v
We have observed that Au nanorods (NRs) have distinct effects on cell viability via killing cancer cells while posing negligible impact on normal cells and mesenchymal stem cells. Obvious differences in cellular uptake, intracellular trafficking, and susceptibility of lysosome to Au NRs by different types of cells resulted in selective accumulation of Au NRs in the mitochondria of cancer cells. Their long-term retention decreased mitochondrial membrane potential and increased reactive oxygen species level that enhances the likelihood of cell death. These findings thus provide guidance for the design of organelle-targeted nanomaterials in tumor therapy.
Co-reporter:Ying Qu, Wei Li, Yunlong Zhou, Xuefeng Liu, Lili Zhang, Liming Wang, Yu-feng Li, Atsuo Iida, Zhiyong Tang, Yuliang Zhao, Zhifang Chai, and Chunying Chen
Nano Letters 2011 Volume 11(Issue 8) pp:3174-3183
Publication Date(Web):July 1, 2011
DOI:10.1021/nl201391e
We evaluated the in vivo fate and physiological behavior of quantum dots (QDs) in Caenorhabditis elegans by GFP transfection, fluorescent imaging, synchrotron radiation based elemental imaging, and speciation techniques. The in situ metabolism and degradation of QDs in the alimentary system and long-term toxicity on reproduction are fully assessed. This work highlights the utility of the C. elegans model as a multiflexible platform to allow noninvasively imaging and monitoring in vivo consequences of engineered nanomaterials.
Co-reporter:Yu-Feng Li, Liang Hu, Bai Li, Xiaohan Huang, Erik H. Larsen, Yuxi Gao, Zhifang Chai and Chunying Chen
Journal of Analytical Atomic Spectrometry 2011 vol. 26(Issue 1) pp:224-229
Publication Date(Web):25 Nov 2010
DOI:10.1039/C0JA00129E
Accurate determination of selenium (Se) species in biological samples is a critical issue because Se commonly occurs at low levels and in diverse species. The method for the full quantification of Se species in serum samples was proposed through combined ion-pair reverse-phase (RP) chromatography and affinity chromatography (AF) hyphenated to inductively coupled plasma-(quadrupole) mass spectrometry (ICP-qMS) with post-column isotope dilution analysis (IDA) and a collision cell technique (CCT). Different Se species like inorganic Se (Se4+ and Se6+), selenocystine (SeCys), selenomethionine (SeMet), selenoprotein P (SelP), selenoalbumin (SeAlb) and glutathione peroxidase (GPx) can be separated and quantified. The proposed methodology was used to qualitatively and quantitatively study the dynamic distribution of Se species in human serum samples from the Hg-contaminated area after supplementation with 100 μg of Se daily as Se-enriched yeast for 180 days. SelP takes up almost half and even more of the total Se and increases with the Se administration. The repeatability in terms of relative standard deviation (R.S.D. %, n = 10) is 6% for GPx and SelP and 5% for SeAlb. The detection limits are 0.1 μg Se L−1 for GPx and other non-retained Se compounds, 1.0 μg Se L−1 for SelP and 1.2 μg Se L−1 for SeAlb, 1.3 μg Se L−1 for inorganic Se; 1.2 μg Se L−1 for SeCys; 1.1 μg Se L−1 for SeMet, respectively.
Co-reporter:Yuexian Liu, Wei Li, Fang Lao, Ying Liu, Liming Wang, Ru Bai, Yuliang Zhao, Chunying Chen
Biomaterials 2011 Volume 32(Issue 32) pp:8291-8303
Publication Date(Web):November 2011
DOI:10.1016/j.biomaterials.2011.07.037
The fate of nanomaterials with different sizes and charges in mitotic cells is of great importance but seldom explored. Herein we investigate the intracellular fate of negatively charged carboxylated polystyrene (COOH–PS) and positively charged amino-modified polystyrene (NH2–PS) nanoparticles of three different diameters (50, 100 and 500 nm) on cancer HeLa cells and normal NIH 3T3 cells during the cell cycles. The results showed that all the fluorescent PS nanoparticles differing in size and/or charge did not interact with chromosome reorganization and cytoskeleton assembly during the mitotic process in live cells. They neither disturbed chromosome reorganization nor affected the cytoskeleton reassembly in both normal and cancer cells. However, NH2–PS at the size of 50 nm caused G1 phase delay and a decrease of cyclin (D, E) expression, respectively. Moreover, NH2–PS displayed higher cellular toxicity and NH2–PS of 50 nm disturbed the integrity of cell membranes. Both cationic and anionic PS nanoparticles had a more pronounced effect on normal NIH 3T3 cells than cancer HeLa cell. Our research provides insight into the dynamic fate, intracellular behavior, and the effects of nanoparticles on spindle and chromosomes during cell division, which will enable the optimization of design and selection of much safer nanoparticles for lower risk to human health and widely medical applications.
Co-reporter:Yan Wu, Fang Jiao, Siyuan Han, Tengfei Fan, Ying Liu, Wei Li, Liming Hu, Yuliang Zhao, Chunying Chen
Nanomedicine: Nanotechnology, Biology and Medicine 2011 Volume 7(Issue 6) pp:945-954
Publication Date(Web):December 2011
DOI:10.1016/j.nano.2011.04.010
Novel amphiphilic copolymer nanoparticles (HPAE-co-PLA-DPPE) composed of hyperbranched poly (amine-ester), polylactide and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE) segments were designed and synthesized that provided high encapsulation efficiency. These nanoparticles (NPs) were used to encapsulate an antitumor model drug, doxorubicin (DOX). The resulting NPs exhibited high encapsulation efficiency to DOX under an appropriate condition. In vitro release experiments revealed that the release of DOX from NPs was faster at pH 4.5 than that at pH 7.4 or pH 6.0. Confocal microscopy observation indicated that the DOX-loaded NPs can enter cells and localize in lysosomes that can be released quickly into the cytoplasm. The DOX-loaded NPs showed comparable anticancer efficacy with the free drug both in vivo and in vitro. These results demonstrate a feasible application of the hyperbranched copolymer, HPAE-co-PLA-DPPE, as a promising nanocarrier for intracellular delivery of antitumor drugs.From the Clinical EditorIn this paper, the development of novel amphiphilic copolymer nanoparticles is discussed with the goal of establishing high encapsulation efficiency for chemotherapy drugs.A novel hyperbranched poly (amine-ester) derivative (HPAE-co-PLA-DPPE) was synthesized by conjugating DPPE onto HPAE-co-PLA. DOX molecules were efficiently loaded into the HPAE-co-PLA-DPPE nanoparticles and rapidly released under acidic conditions with higher anti-tumor ability both in vitro and in vivo. These data show that pH-responsive HPAE-co-PLA-DPPE conjugate nanoparticles efficiently deliver anticancer drugs.
Co-reporter:Weiwei He, Ying Liu, Jinshan Yuan, Jun-Jie Yin, Xiaochun Wu, Xiaona Hu, Ke Zhang, Jianbo Liu, Chunying Chen, Yinglu Ji, Yuting Guo
Biomaterials 2011 32(4) pp: 1139-1147
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.09.040
Co-reporter:Wei Li, Lina Zhao, Taotao Wei, Yuliang Zhao, Chunying Chen
Biomaterials 2011 32(16) pp: 4030-4041
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.02.008
Co-reporter:Jiangfeng Du;Cuicui Ge;Lina Zhao;Liming Wang;Denghua Li;Yanlian Yang;Yuliang Zhao;Ruhong Zhou;Zhifang Chai;Ying Liu
PNAS 2011 Volume 108 (Issue 41 ) pp:
Publication Date(Web):2011-10-11
DOI:10.1073/pnas.1105270108
With the potential wide uses of nanoparticles such as carbon nanotubes in biomedical applications, and the growing concerns
of nanotoxicity of these engineered nanoparticles, the importance of nanoparticle–protein interactions cannot be stressed
enough. In this study, we use both experimental and theoretical approaches, including atomic force microscope images, fluorescence
spectroscopy, CD, SDS-PAGE, and molecular dynamics simulations, to investigate the interactions of single-wall carbon nanotubes
(SWCNTs) with human serum proteins, and find a competitive binding of these proteins with different adsorption capacity and
packing modes. The π-π stacking interactions between SWCNTs and aromatic residues (Trp, Phe, Tyr) are found to play a critical role in determining
their adsorption capacity. Additional cellular cytotoxicity assays, with human acute monocytic leukemia cell line and human
umbilical vein endothelial cells, reveal that the competitive bindings of blood proteins on the SWCNT surface can greatly
alter their cellular interaction pathways and result in much reduced cytotoxicity for these protein-coated SWCNTs, according
to their respective adsorption capacity. These findings have shed light toward the design of safe carbon nanotube nanomaterials
by comprehensive preconsideration of their interactions with human serum proteins.
Co-reporter:Fang Jiao, Ying Liu, Ying Qu, Wei Li, Guoqiang Zhou, Cuicui Ge, Yufeng Li, Baoyun Sun, Chunying Chen
Carbon 2010 Volume 48(Issue 8) pp:2231-2243
Publication Date(Web):July 2010
DOI:10.1016/j.carbon.2010.02.032
The purpose was to examine the anti-tumor and antimetastatic activities of fullerenol and their related mechanisms. Thirty EMT-6 tumor-bearing mice were injected intraperitoneally with 0.1 ml saline or 0.1 ml saline containing fullerenol C60(OH)20 (0.08 and 0.4 mg/ml) daily for 16 days. Using tumor tissues, we investigated imbalances in the oxidative defense system and the expression of several angiogenesis factors. C60(OH)20 exhibits anti-tumor and antimetastatic activities in EMT-6 breast cancer metastasis model. Treatment with C60(OH)20 was found to modulate oxidative stress significantly. The expression of several angiogenesis factors was reduced in tumor tissues after treatment with fullerenol. Importantly, CD31 (also known as PECAM-1, platelet endothelial cell adhesion molecule) expression and vessel density were markedly reduced in tumors from fullerenol-treated mice compared with controls. Modulation of oxidative stress in tumor tissues, inhibition of the formation of angiogenesis factors, and subsequent reduction in tumor vessel density and the nutrient supply to tumor cells could be important mechanisms by which fullerenol aggregates inhibit tumor growth and suppress carcinoma metastasis in vivo.
Co-reporter:Liming Wang;Yu-Feng Li;Liangjun Zhou;Ying Liu
Analytical and Bioanalytical Chemistry 2010 Volume 396( Issue 3) pp:1105-1114
Publication Date(Web):2010 February
DOI:10.1007/s00216-009-3302-y
Integrated analytical techniques were used to study the tissue distribution and structural information of gold nanorods (Au NRs) in Sprague-Dawley rats through tail intravenous injection. Before in vivo experiments were conducted, careful characterization of Au NRs was performed. The zeta potential proved that adsorption of bovine serum albumin on Au NRs turned the surface charges from positive to negative as in an in vitro simulation. The biodistribution of Au NRs was investigated quantitatively by inductively coupled plasma mass spectrometry at different time points after injection. As target tissues, both liver and spleen were chosen to further demonstrate the intracellular localization of Au NRs by the combination of transmission electron microscopy and energy-dispersive X-ray spectroscopy. Moreover, synchrotron-radiation-based X-ray absorption spectroscopy was employed and it was observed that long-term retention of Au NRs in liver and spleen did not induce obvious changes in the oxidation states of gold. Therefore, the present systematic method can provide important information about the fates of Au NRs in vivo and can also be extended to study the biological effects of other metallic nanomaterials in the future.
Co-reporter:XiaoHui Li;Cheng Zhang;Laurent Le Guyader
Science China Chemistry 2010 Volume 53( Issue 11) pp:2241-2249
Publication Date(Web):2010 November
DOI:10.1007/s11426-010-4122-9
Recent development in nanotechnology has provided new tools for cancer therapy and diagnostics. Because of their small size, nanoscale devices readily interact with biomolecules both on the cell surface and inside the cell. Nanomaterials, such as fullerenes and their derivatives, are effective in terms of interactions with the immune system and have great potential as anticancer drugs. Comparatively, other nanomaterials are able to load active drugs to cancer cells by selectively using the unique tumor environment, such as their enhanced permeability, retention effect and the specific acidic microenvironment. Multifunctional and multiplexed nanoparticles, as the next generation of nanoparticles, are now being extensively investigated and are promising tools to achieve personalized and tailored cancer treatments.
Co-reporter:Yang Qiu, Ying Liu, Liming Wang, Ligeng Xu, Ru Bai, Yinglu Ji, Xiaochun Wu, Yuliang Zhao, Yufeng Li, Chunying Chen
Biomaterials 2010 31(30) pp: 7606-7619
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.06.051
Co-reporter:Fang Lao, Long Chen, Wei Li, Cuicui Ge, Ying Qu, Quanmei Sun, Yuliang Zhao, Dong Han and Chunying Chen
ACS Nano 2009 Volume 3(Issue 11) pp:3358
Publication Date(Web):October 19, 2009
DOI:10.1021/nn900912n
There is a dearth in fundamental cellular-level understanding of how nanoparticles interact with the cells of the blood brain barrier (BBB), particularly under the oxidative environment. The apoptosis of cerebral microvessel endothelial cells (CMECs) induced by oxidative stress injury plays a key role in the dysfunction of BBB. By use of CMECs as an in vitro BBB model, we show for the first time that C60(C(COOH)2)2 nanoparticles can selectively enter oxidized CMECs rather than normal cells, and maintain CMECs integrity by attenuating H2O2-induced F-actin depolymerization via the observation of several state-of-the art microscopic techniques. Additionally, we have found that C60(C(COOH)2)2 nanoparticles greatly inhibit the apoptosis of CMECs induced by H2O2, which is related to their modulation of the JNK pathway. C60(C(COOH)2)2 nanoparticles can regulate several downstream signaling events related to the JNK pathway, including reduction of JNK phosphorylation, activation of activator protein 1 (AP-1) and caspase-3, and inhibition of polyADP-ribose polymerase (PARP) cleavage and mitochondrial cytochrome c release. Our results indicate that C60(C(COOH)2)2 nanoparticles possess a novel ability of selectively entering oxidation-damaged cerebral endothelial cells rather than normal endothelial cells and then protecting them from apoptosis.Keywords: apoptosis; C60(C(COOH)2)2; JNK pathway; microvessel endothelial cells; oxidative injury
Co-reporter:Yan Zhang;Bai Li;Zhonghong Gao
BioMetals 2009 Volume 22( Issue 2) pp:251-259
Publication Date(Web):2009 April
DOI:10.1007/s10534-008-9161-8
Subcellular distribution of metal-containing proteins of Fe, Cu, Zn and Cd were determined in the liver samples of iron overload mice by size exclusion high performance liquid chromatography with on-line coupling to UV and inductively coupled plasma mass spectrometry. Collision cell techniques was used to remove polyatomic interferences for some elements, such as Fe. Comparative molecular weight (MW) information of the elemental fraction was obtained within a retention time of 40 min. Fe was present only in high-MW (HMW) protein; Cu, Zn and Cd were found in different MW proteins. It was also observed that these four elements studied showed predominant association with HMW fractions. Moreover, compared with the normal group, we found that the contents of these elements except Cu significantly increased and the distribution of some elements like Cd changed in iron overload mouse liver. It means that excessive iron accumulation in vivo may affect the metabolism of other element such as Zn and Cd.
Co-reporter:Jun-Jie Yin, Fang Lao, Peter P. Fu, Wayne G. Wamer, Yuliang Zhao, Paul C. Wang, Yang Qiu, Baoyun Sun, Gengmei Xing, Jinquan Dong, Xing-Jie Liang, Chunying Chen
Biomaterials 2009 Volume 30(Issue 4) pp:611-621
Publication Date(Web):February 2009
DOI:10.1016/j.biomaterials.2008.09.061
We demonstrated that three different types of water-soluble fullerenes materials can intercept all of the major physiologically relevant ROS. C60(C(COOH)2)2, C60(OH)22, and Gd@C82(OH)22 can protect cells against H2O2-induced oxidative damage, stabilize the mitochondrial membrane potential and reduce intracellular ROS production with the following relative potencies: Gd@C82(OH)22 ≥ C60(OH)22 > C60(C(COOH)2)2. Consistent with their cytoprotective abilities, these derivatives can scavenge the stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH), and the reactive oxygen species (ROS) superoxide radical anion (O2−), singlet oxygen, and hydroxyl radical (HO), and can also efficiently inhibit lipid peroxidation in vitro. The observed differences in free radical-scavenging capabilities support the hypothesis that both chemical properties, such as surface chemistry induced differences in electron affinity, and physical properties, such as degree of aggregation, influence the biological and biomedical activities of functionalized fullerenes. This represents the first report that different types of fullerene derivatives can scavenge all physiologically relevant ROS. The role of oxidative stress and damage in the etiology and progression of many diseases suggests that these fullerene derivatives may be valuable in vivo cytoprotective and therapeutic agents.
Co-reporter:Cuicui Ge, Fang Lao, Wei Li, Yufeng Li, Chunying Chen, Yang Qiu, Xueying Mao, Bai Li, Zhifang Chai and Yuliang Zhao
Analytical Chemistry 2008 Volume 80(Issue 24) pp:9426
Publication Date(Web):November 11, 2008
DOI:10.1021/ac801469b
Metal impurities in carbon nanotubes (CNTs) are undesirable for their uses in diverse applications, for instance, they may potentially have a negative health impact when using in biomedical fields. However, so far there is a lack of analysis methods able to quantify metallic impurities in CNTs. In this paper, using the neutron activation analysis (NAA) technique as a nondestructive standard quantification method and inductively coupled plasma mass spectrometry (ICPMS) as a practical approach, we established an analytical method for quantitative determination of metallic impurities in CNTs. ICPMS, one of the most sensitive analytical techniques used for coincident multielement measurements, has become a common tool in many laboratory, and thus it is easily available and a good selection for determining the metal impurities in CNTs. However, because of their extremely stable structure and the encapsulated metals in the defect structure, CNTs must undergo special pretreatments before ICPMS. We investigated different sample pretreatment procedures for ICPMS analysis, including dry ashing coupled with acid extraction, wet digestion, and a combination of dry ashing with acid digestion. With the reference data from the nondestructive analytical method of NAA, we found that the quantitative determination of metal impurities in CNTs is highly dependent on the sample pretreatment in which the conditions are largely different from those used for conventional biological samples or environmental materials. This paper not only provides the practical method and analysis conditions for quantifying the metal impurities of CNTs but also the first protocol for pretreatment processes of CNT samples.
Co-reporter:Yu-Feng Li, Chunying Chen, Bai Li, Wei Li, Liya Qu, Zeqin Dong, Masaharu Nomura, Yuxi Gao, Jinxuan Zhao, Wei Hu, Yuliang Zhao, Zhifang Chai
Journal of Inorganic Biochemistry 2008 Volume 102(Issue 3) pp:500-506
Publication Date(Web):March 2008
DOI:10.1016/j.jinorgbio.2007.11.005
Human hair and blood samples from persons living in the town of Wanshan, a mercury mine area in Guizhou Province of China, were collected and the quantitative speciation and structural information of Hg and S in hair samples and of Hg in erythrocyte and serum samples were studied using X-ray absorption spectroscopy. Least-squares fitting of the X-ray absorption near-edge spectra found that inorganic mercury is the major mercury species in hair samples (91.74%), while inorganic and methyl mercury are both about 50% of total mercury in RBC and serum samples, which is in agreement with the data obtained by acidic extraction, fractionation of Hg2+ and CH3Hg+ and quantification by ICP-MS. Curve-fitting analysis revealed that the Hg–S bond length and coordination number in hair were 0.248 ± 0.002 nm and 3.10, respectively, while the S–Hg bond length and coordination number in hair were 0.236 ± 0.002 nm and 4.05. The Hg–S bond length and coordination number in RBC were 0.251 ± 0.003 nm and 4.09, respectively, while they were 0.228 ± 0.002 nm and 4.08 in serum, respectively. The techniques for speciation, structural and binding information described in this study will find the potential application in similar studies of other elements.
Co-reporter:Yuxi Gao, Nianqing Liu, Chunying Chen, Yunfeng Luo, Yufeng Li, Zhiyong Zhang, Yuliang Zhao, Baolu Zhao, Atsuo Iida and Zhifang Chai
Journal of Analytical Atomic Spectrometry 2008 vol. 23(Issue 8) pp:1121-1124
Publication Date(Web):25 Jun 2008
DOI:10.1039/B802338G
To investigate the toxicological effects of nanomaterials, experimental studies on the absorption and accumulation in organisms are of broad interest. In the present study, Caenorhabditis elegans (C. elegans) was used as a “model” organism to investigate the bioaccumulation and toxicological effects of engineered copper nanoparticles with a scanning technique of microbeam synchrotron radiation X-ray fluorescence (μ-SRXRF). The adult hermaphrodite is anatomically simple with 959 somatic cells and 1 mm in length. The mapping results of the whole organism indicate that the exposure to copper nanoparticles can result in an obvious elevation of Cu and K levels, and a change of bio-distribution of Cu in nematodes. Accumulation of Cu occurs in the head and at a location 1/3 of the way up the body from the tail compared to the un-exposed control. In contrast, a higher amount of Cu was detected in other portion of worm body, especially in its excretory cells and intestine when exposed to Cu2+. The results compared well with total Cu levels in nematodes, which were 4.10 ± 0.54, 12.32 ± 0.49 and 5.22 ± 0.63 μg g−1 dry weight for the PBS, Cu2+ and Cu nanoparticle groups, respectively, measured by ICP-MS. The nondestructive and multi-elemental μ-SRXRF provides an important tool for mapping the elemental distribution in the whole body of a single tiny nematode at lower levels.
Co-reporter:Yu-Feng Li, Chunying Chen, Bai Li, Qing Wang, Jiangxue Wang, Yuxi Gao, Yuliang Zhao and Zhifang Chai
Journal of Analytical Atomic Spectrometry 2007 vol. 22(Issue 8) pp:925-930
Publication Date(Web):26 Jun 2007
DOI:10.1039/B703310A
The present study was carried out to establish a method for simultaneous speciation analysis of selenium and mercury. Batch-wise elution using two different mobile phases that are suitable for selenium and mercury speciation leads to successful determination of both selenium and mercury standards in 30 minutes with good efficiency and resolution. The detection limits are in the range of 0.05–0.3 μg L−1 for selenium species, except TMSe, which has a poorer detection limit (1.48 μg L−1), and 2.5 μg L−1 for inorganic mercury (Hg2+) and 2.0 μg L−1 for organic mercury (CH3Hg+). The method was applied to analysis of urine samples from people who were long-term mercury exposed and supplemented with selenium-enriched yeast for 90 days. Selenocystine (SeCys) was found to be a major selenium form, while inorganic mercury is the major mercury form. The recoveries of spiked species were between 93 and 117% in all cases. The increased mercury concentrations in urine after 90-day selenium supplementation suggest that selenium is beneficial to the excretion of mercury from urine. The proposed technique may help to increase our understanding of the in vivo interaction between selenium and mercury in human body.
Co-reporter:Yu-Feng Li, Chunying Chen, Bai Li, Jiangxue Wang, Yuxi Gao, Yuliang Zhao, Zhifang Chai
Environmental Research (May 2008) Volume 107(Issue 1) pp:39-44
Publication Date(Web):1 May 2008
DOI:10.1016/j.envres.2007.07.003
Hair is a well-established and widely used matrix for measuring mercury exposure of an individual. Although a variety of washing procedures to remove external mercury contamination have been proposed, no standardized procedures are available yet. In this study, different washing reagents like l-cysteine (Cys), 2-mercaptoethanol (ME), and disodium diaminoethanetetra acetate (EDTA) were used to find out if it is possible to remove mercury contamination from human scalp hair spiked with HgCl2 solutions at different concentrations. It was found that the external mercury contamination could not be fully washed off even using reagents with high affinity to mercury like l-cysteine and ME. However, for the well-pulverized CRM hair samples some of the endogenous mercury was washed off. It suggests that hair is not a suitable biomarker for evaluation of total mercury exposure especially in people like mercury miners or gold miners/burners associated with serious external Hg exposure. However, hair still can be used as an indicator for methyl mercury exposure because, generally, there is almost no exogenous contamination of methyl mercury in hair.
Co-reporter:Jabran Saleem, Liming Wang, Chunying Chen
NanoImpact (January 2017) Volume 5() pp:109-118
Publication Date(Web):1 January 2017
DOI:10.1016/j.impact.2017.01.005
•GFNs can suppress or activate immune system, depending on physicochemical properties and functionalization.•Immunomodulation may realize biomedical applications.Graphene and its derivatives are called graphene family nanomaterials (GFNs). Over the past few years, they have been heavily investigated in biomedical arena due to their extraordinary physiochemical properties and potential biomedical applications. However, the biocompatibility of GFNs is becoming important for biomedical applications such as drug and gene delivery, tissue engineering, biosensing and imaging. In this regard, it is crucial to understand the process of interaction of GFNs with immune system, which is also meaningful to manipulate their interaction for safe and efficient applications. Herein, different modalities of GFNs interaction with various components of immune system and the outcome of these interactions are described and evaluated. This review also summarizes different mechanisms involved in immunological effects of GFNs and techniques that are employed for GFNs, to escape the clutches of immune system. We elucidate the intricate balance between immune-stimulation and immune-suppression and expect that understanding of immunological effects of graphene derivatives would help evaluate and estimate the possible biomedical applications as far as immune system is concerned.Download high-res image (170KB)Download full-size image
Co-reporter:Chunying Chen, Jing Liu, Jing Wang, Xiaochun Wu, Zhanjun Gu
Nanomedicine: Nanotechnology, Biology and Medicine (February 2016) Volume 12(Issue 2) pp:455
Publication Date(Web):February 2016
DOI:10.1016/j.nano.2015.12.023
Co-reporter:Chunying Chen, Jing Liu, Jing Wang, Xiaochun Wu, Zhanjun Gu
Nanomedicine: Nanotechnology, Biology and Medicine (February 2016) Volume 12(Issue 2) pp:455
Publication Date(Web):February 2016
DOI:10.1016/j.nano.2015.12.023
Co-reporter:Xiaoyan Wang, Yu-Feng Li, Bai Li, Zeqin Dong, Liya Qu, Yuxi Gao, Zhifang Chai, Chunying Chen
Applied Geochemistry (February 2011) Volume 26(Issue 2) pp:
Publication Date(Web):1 February 2011
DOI:10.1016/j.apgeochem.2010.11.017
Potentially harmful element contamination from mining and smelting raises concerns due to possible health risks. For most people, diet is the main route of exposure to potentially harmful elements, so determination of the concentrations of these elements in foodstuffs and assessment of their possible risk for humans via dietary intake is very important. This study was designed to investigate the concentrations of different elements, including Hg, Pb, Cd, Mn and Se in foodstuffs and to estimate the potential health risk of these elements via consumption of polluted foodstuffs in the Wanshan Hg mine area, Guizhou province, SW China. The multielemental concentrations were determined by inductively coupled plasma-mass spectrometry (ICP-MS). The target hazard quotient (THQ) and hazard index (HI) were calculated to evaluate the potential health risk from individual and combined potentially harmful elements due to dietary intake. The average contents of Hg, Pb, Cd, Mn and Se in the most frequently consumed foodstuffs were: 31, 248, 121, 1035 and 32 μg/kg respectively. Among them, Cd and Hg were the most important contributors to potentially harmful elements contamination in Wanshan. Eight of 10 kinds of vegetables were contaminated to various levels by different elements but the samples of rice, pork, radish and potato were below the stipulated limits for toxic elements. In this study, the average dietary intakes of Hg, Pb, Cd, Mn, Se by an adult man of 60 kg living in Wanshan were: 27, 167, 86, 1061, 42 μg/day, respectively. The HIs for multielement dietary intake was 3.11, with the relative contributions of Hg, Pb, Cd, Mn and Se being 22.3%, 24.3%, 45.0%, 3.9% and 4.4%, respectively, which indicated that consumption of food poses a potential health risk. Vegetables were found to be the main source of potentially harmful element dietary intake.Research highlights► Wanshan is the most important historical Hg mining area in China. ► Foodstuffs from Wanshan is collected and Hg, Pb, Cd, Mn and Se were determined. ► Cd and Hg were the most important contributors. ► Vegetables were the main source of potentially harmful element dietary intake. ► Consumption of local foodstuffs poses a potential health risk.
Co-reporter:Rui Chen, Bin Hu, Ying Liu, Jianxun Xu, Guosheng Yang, Diandou Xu, Chunying Chen
Biochimica et Biophysica Acta (BBA) - General Subjects (December 2016) Volume 1860(Issue 12) pp:
Publication Date(Web):1 December 2016
DOI:10.1016/j.bbagen.2016.03.019
•High concentration ultrafine particles in urban area constitute realistic health impacts.•Extremely small size and large particle number of UFPs dominate the high toxicity in PM2.5.•Knowledge from nanotoxicology provides insights to understand toxic effects of UFPs.•Airway mucosa constitutes the first barrier to UFPs exposure in respiratory system.BackgroundAir pollution constitutes the major threat to human health, whereas their adverse impacts and underlying mechanisms of different particular matters are not clearly defined.Scope of reviewUltrafine particles (UFPs) are high related to the anthropogenic emission sources, i.e. combustion engines and power plants. Their composition, source, typical characters, oxidative effects, potential exposure routes and health risks were thoroughly reviewed.Major conclusionsUFPs play a major role in adverse impacts on human health and require further investigations in future toxicological research of air pollution.General significanceUnlike PM2.5, UFPs may have much more impacts on human health considering loads of evidences emerging from particulate matters and nanotoxicology research fields. The knowledge of nanotoxicology contributes to the understanding of toxicity mechanisms of airborne UFPs in air pollution. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu.
Co-reporter:Jinxia Li, Feng Zhao, Chunying Chen
Science Bulletin (December 2016) Volume 61(Issue 23) pp:1788-1790
Publication Date(Web):1 December 2016
DOI:10.1007/s11434-016-1203-y
Co-reporter:Li Meng, Aihua Jiang, Rui Chen, Chen-zhong Li, Liming Wang, Ying Qu, Peng Wang, Yuliang Zhao, Chunying Chen
Toxicology (8 November 2013) Volume 313(Issue 1) pp:49-58
Publication Date(Web):8 November 2013
DOI:10.1016/j.tox.2012.11.011
The increasing use of carbon nanotubes (CNTs) in biomedical applications has garnered a great concern on their potential negative effects to human health. CNTs have been reported to potentially disrupt normal neuronal function and they were speculated to accumulate and cause brain damage, although a lot of distinct and exceptional properties and potential wide applications have been associated with this material in neurobiology. Fe impurities strapped inside the CNTs may be partially responsible for neurotoxicity generation. In the present study, we selected rat pheochromocytoma (PC12) cells to investigate and compare the effects of two kinds of multiwall carbon nanotubes (MWCNTs) with different concentrations of Fe impurities which usually come from the massive production of CNTs by chemical vapor deposition. Exposure to Fe-high MWCNTs can reduce cell viability and increase cytoskeletal disruption of undifferentiated PC12 cells, diminish the ability to form mature neurites, and then adversely influence the neuronal dopaminergic phenotype in NGF-treated PC-12 cells. The present results highlight the critical role of iron residue in the adverse response to MWCNTs exposure in neural cells. These findings provide useful information for understanding the toxicity and safe application of carbon nanotubes.
Co-reporter:Jiangxue Wang, Ying Liu, Fang Jiao, Fang Lao, Wei Li, Yiqun Gu, Yufeng Li, Cuicui Ge, Guoqiang Zhou, Bai Li, Yuliang Zhao, Zhifang Chai, Chunying Chen
Toxicology (5 December 2008) Volume 254(Issues 1–2) pp:82-90
Publication Date(Web):5 December 2008
DOI:10.1016/j.tox.2008.09.014
Nanoparticles can be administered via nasal, oral, intraocular, intratracheal (pulmonary toxicity), tail vein and other routes. Here, we focus on the time-dependent translocation and potential damage of TiO2 nanoparticles on central nervous system (CNS) through intranasal instillation. Size and structural properties are important to assess biological effects of TiO2 nanoparticles. In present study, female mice were intranasally instilled with two types of well-characterized TiO2 nanoparticles (i.e. 80 nm, rutile and 155 nm, anatase; purity > 99%) every other day. Pure water instilled mice were served as controls. The brain tissues were collected and evaluated for accumulation and distribution of TiO2, histopathology, oxidative stress, and inflammatory markers at post-instillation time points of 2, 10, 20 and 30 days. The titanium contents in the sub-brain regions including olfactory bulb, cerebral cortex, hippocampus, and cerebellum were determined by inductively coupled plasma mass spectrometry (ICP-MS). Results indicated that the instilled TiO2 directly entered the brain through olfactory bulb in the whole exposure period, especially deposited in the hippocampus region. After exposure for 30 days, the pathological changes were observed in the hippocampus and olfactory bulb using Nissl staining and transmission electron microscope. The oxidative damage expressed as lipid peroxidation increased significantly, in particular in the exposed group of anatase TiO2 particles at 30 days postexposure. Exposure to anatase TiO2 particles also produced higher inflammation responses, in association with the significantly increased tumor necrosis factor alpha (TNF-α) and interleukin (IL-1β) levels. We conclude that subtle differences in responses to anatase TiO2 particles versus the rutile ones could be related to crystal structure. Thus, based on these results, rutile ultrafine-TiO2 particles are expected to have a little lower risk potential for producing adverse effects on central nervous system. Although understanding the mechanisms requires further investigation, the present results suggest that we should pay attention to potential risk of occupational exposure for large-scaled production of TiO2 nanoparticles.
Co-reporter:Liming Wang, Chunying Chen
Toxicology and Applied Pharmacology (15 May 2016) Volume 299() pp:30-40
Publication Date(Web):15 May 2016
DOI:10.1016/j.taap.2016.01.022
•Rapid protein adsorption onto nanomaterials that affects biomedical effects•Nanomaterials and their interaction with biological membrane, intracellular trafficking and specific cellular effects•Nanomaterials and their interaction with biological barriers•The signaling pathways mediated by nanomaterials and related biomedical effects•Novel techniques for studying translocation and biomedical effects of NMsNanomaterials (NMs) have been widespread used in biomedical fields, daily consuming, and even food industry. It is crucial to understand the safety and biomedical efficacy of NMs. In this review, we summarized the recent progress about the physiological and pathological effects of NMs from several levels: protein-nano interface, NM-subcellular structures, and cell–cell interaction. We focused on the detailed information of nano-bio interaction, especially about protein adsorption, intracellular trafficking, biological barriers, and signaling pathways as well as the associated mechanism mediated by nanomaterials. We also introduced related analytical methods that are meaningful and helpful for biomedical effect studies in the future. We believe that knowledge about pathophysiologic effects of NMs is not only significant for rational design of medical NMs but also helps predict their safety and further improve their applications in the future.
Co-reporter:Jiangxue Wang, Chunying Chen, Ying Liu, Fang Jiao, Wei Li, Fang Lao, Yufeng Li, Bai Li, Cuicui Ge, Guoqiang Zhou, Yuxi Gao, Yuliang Zhao, Zhifang Chai
Toxicology Letters (15 December 2008) Volume 183(Issues 1–3) pp:72-80
Publication Date(Web):15 December 2008
DOI:10.1016/j.toxlet.2008.10.001
Nanoscale titanium dioxide (TiO2) is massively produced and widely used in living environment, which hence make the potential risk to human health. Central nervous system (CNS) is the potential susceptible target of inhaled nanoparticles, but the studies on this aspect are limited so far. We report the accumulation and toxicity results in vivo of two crystalline phases of TiO2 nanoparticles (80 nm, rutile and 155 nm, anatase; purity >99%). The female mice were intranasally instilled with 500 μg of TiO2 nanoparticles suspension every other day for 30 days. Synchrotron radiation X-ray fluorescence analysis (SRXRF) and inductively coupled plasma mass spectrometry (ICP–MS) were used to determine the contents of titanium in murine brain. Then, the pathological examination of brain tissue, oxidative stress-mediated responses, and levels of neurochemicals in the brain of exposed mice were also analyzed. The obvious morphological changes of hippocampal neurons and increased GFAP-positive astrocytes in the CA4 region were observed, which were in good agreements with higher Ti contents in the hippocampus region. Oxidative stress occurred obviously in whole brain of exposed mice such as lipid peroxidation, protein oxidation and increased activities of catalase, as well as the excessive release of glutamic acid and nitric oxide. These findings indicate anatase TiO2 nanoparticles exhibited higher concern on some tested biological effects. To summarize, results provided the preliminary evidence that nasal instilled TiO2 nanoparticles could be translocated into the central nervous system and cause potential lesion of brain, and the hippocampus would be the main target within brain.
Co-reporter:Lili Zhang, Ru Bai, Bai Li, Cuicui Ge, Jiangfeng Du, Ying Liu, Laurent Le Guyader, Yuliang Zhao, Yanchuan Wu, Shida He, Yongmei Ma, Chunying Chen
Toxicology Letters (10 November 2011) Volume 207(Issue 1) pp:73-81
Publication Date(Web):10 November 2011
DOI:10.1016/j.toxlet.2011.08.001
The rising commercial use and large-scale production of engineered nanoparticles (NPs) may lead to unintended exposure to humans. The central nervous system (CNS) is a potential susceptible target of the inhaled NPs, but so far the amount of studies on this aspect is limited. Here, we focus on the potential neurological lesion in the brain induced by the intranasally instilled titanium dioxide (TiO2) particles in rutile phase and of various sizes and surface coatings. Female mice were intranasally instilled with four different types of TiO2 particles (i.e. two types of hydrophobic particles in micro- and nano-sized without coating and two types of water-soluble hydrophilic nano-sized particles with silica surface coating) every other day for 30 days. Inductively coupled plasma mass spectrometry (ICP-MS) were used to determine the titanium contents in the sub-brain regions. Then, the pathological examination of brain tissues and measurements of the monoamine neurotransmitter levels in the sub-brain regions were performed. We found significant up-regulation of Ti contents in the cerebral cortex and striatum after intranasal instillation of hydrophilic TiO2 NPs. Moreover, TiO2 NPs exposure, in particular the hydrophilic NPs, caused obvious morphological changes of neurons in the cerebral cortex and significant disturbance of the monoamine neurotransmitter levels in the sub-brain regions studied. Thus, our results indicate that the surface modification of the NPs plays an important role on their effects on the brain. In addition, the difference in neurotoxicity of the two types of hydrophilic NPs may be induced by the shape differences of the materials. The present results suggest that physicochemical properties like size, shape and surface modification of the nanomaterials should be considered when evaluating their neurological effects.Highlights► We compare the potential neurotoxicity of four different types of TiO2 particles in vivo. ► TiO2 nanoparticles pose greater neurotoxicity than the larger counterpart. ► Hydrophilic TiO2 nanoparticles are more toxic than the hydrophobic ones with similar size. ► Shape difference of nanoparticles may induce different neurotoxicity. ► The physicochemical properties of nanomaterials such as size, shape and surface modification should be considered when evaluating their neurological effects.
Co-reporter:Ying Liu, Chunying Chen
Advanced Drug Delivery Reviews (1 August 2016) Volume 103() pp:76-89
Publication Date(Web):1 August 2016
DOI:10.1016/j.addr.2016.02.010
HIV/AIDS is one of the worst crises affecting global health and influencing economic development and social stability. Preventing and treating HIV infection is a crucial task. However, there is still no effective HIV vaccine for clinical application. Nanotechnology has the potential to solve the problems associated with traditional HIV vaccines. At present, various nano-architectures and nanomaterials can function as potential HIV vaccine carriers or adjuvants, including inorganic nanomaterials, liposomes, micelles and polymer nanomaterials. In this review, we summarize the current progress in the use of nanotechnology for the development of an HIV/AIDS vaccine and discuss its potential to greatly improve the solubility, permeability, stability and pharmacokinetics of HIV vaccines.Although nanotechnology holds great promise for applications in HIV/AIDS vaccines, there are still many inadequacies that result in a variety of risks and challenges. The potential hazards to the human body and environment associated with some nano-carriers, and their underlying mechanisms require in-depth study. Non-toxic or low-toxic nanomaterials with adjuvant activity have been identified. However, studying the confluence of factors that affect the adjuvant activity of nanomaterials may be more important for the optimization of the dosage and immunization strategy and investigations into the exact mechanism of action. Moreover, there are no uniform standards for investigations of nanomaterials as potential vaccine adjuvants. These limitations make it harder to analyze and deduce rules from the existing data. Developing vaccine nano-carriers or adjuvants with high benefit–cost ratios is important to ensure their broad usage. Despite some shortcomings, nanomaterials have great potential and application prospects in the fields of AIDS treatment and prevention.Nanotechnology could solve the problems that perplexing the traditional HIV vaccines. Various nanomaterials have been used as potential vaccine carriers or adjuvant in animal studies. For non-toxic or low-toxic nanomaterials with adjuvant activity, it seems more important to study a confluence of factors that affect the adjuvant activity and optimize the dosage and immunization strategy.Download high-res image (376KB)Download full-size image
Co-reporter:Liming Wang; Qiang Sun; Xin Wang; Tao Wen; Jun-Jie Yin; Pengyang Wang; Ru Bai; Xiang-Qian Zhang; Lu-Hua Zhang; An-Hui Lu
Journal of the American Chemical Society () pp:
Publication Date(Web):January 17, 2015
DOI:10.1021/ja511560b
Under evolutionary pressure from chemotherapy, cancer cells develop resistance characteristics such as a low redox state, which eventually leads to treatment failures. An attractive option for combatting resistance is producing a high concentration of produced free radicals in situ. Here, we report the production and use of dispersible hollow carbon nanospheres (HCSs) as a novel platform for delivering the drug doxorubicine (DOX) and generating additional cellular reactive oxygen species using near-infrared laser irradiation. These irradiated HCSs catalyzed sufficiently persistent free radicals to produce a large number of heat shock factor-1 protein homotrimers, thereby suppressing the activation and function of resistance-related genes. Laser irradiation also promoted the release of DOX from lysosomal DOX@HCSs into the cytoplasm so that it could enter cell nuclei. As a result, DOX@HCSs reduced the resistance of human breast cancer cells (MCF-7/ADR) to DOX through the synergy among photothermal effects, increased generation of free radicals, and chemotherapy with the aid of laser irradiation. HCSs can provide a unique and versatile platform for combatting chemotherapy-resistant cancer cells. These findings provide new clinical strategies and insights for the treatment of resistant cancers.
Co-reporter:Xin Nie, Jiakun Zhang, Qing Xu, Xiaoguang Liu, Yaping Li, Yan Wu and Chunying Chen
Journal of Materials Chemistry A 2014 - vol. 2(Issue 21) pp:NaN3242-3242
Publication Date(Web):2014/03/03
DOI:10.1039/C3TB21744B
In this paper, we report a novel targeting drug delivery system, obtained using an amphiphilic chitosan-co-(D,L-lactide)/1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine copolymer (CS-co-PLA/DPPE) with the modification of an iRGD (CRGDKGPDC) peptide as the targeting module. Hydrophilic doxorubicin (DOX) was encapsulated and cell experiments were carried out to evaluate the anti-tumor efficacy of DOX-loaded nanoparticles (NPs) in vitro. Characterization data showed a favorable size distribution, high encapsulation efficiency and a pH-dependent release profile for the synthesized NPs. A cytotoxicity assay revealed the higher inhibitory effect of DOX–iRGD–NPs especially in cell lines with an abundant expression of αvβ3 integrin receptors. An increased cellular uptake of DOX–iRGD–NPs was observed and further confirmed to be a consequence of a specific endocytosis pathway mediated by ligand–receptor interactions. Visualization of the intracellular trafficking showed different distributions of DOX when delivered using DOX–NPs and DOX–iRGD–NPs, proving the targeting effect of iRGD. With the help of the iRGD targeting peptide, a chemotherapeutic drug can be delivered specifically to the cancer and endothelial cells expressing αvβ3 integrin receptors to achieve an enhanced anti-tumor efficacy and controlled drug release.
Co-reporter:Yuxi Gao, Nianqing Liu, Chunying Chen, Yunfeng Luo, Yufeng Li, Zhiyong Zhang, Yuliang Zhao, Baolu Zhao, Atsuo Iida and Zhifang Chai
Journal of Analytical Atomic Spectrometry 2008 - vol. 23(Issue 8) pp:NaN1124-1124
Publication Date(Web):2008/06/25
DOI:10.1039/B802338G
To investigate the toxicological effects of nanomaterials, experimental studies on the absorption and accumulation in organisms are of broad interest. In the present study, Caenorhabditis elegans (C. elegans) was used as a “model” organism to investigate the bioaccumulation and toxicological effects of engineered copper nanoparticles with a scanning technique of microbeam synchrotron radiation X-ray fluorescence (μ-SRXRF). The adult hermaphrodite is anatomically simple with 959 somatic cells and 1 mm in length. The mapping results of the whole organism indicate that the exposure to copper nanoparticles can result in an obvious elevation of Cu and K levels, and a change of bio-distribution of Cu in nematodes. Accumulation of Cu occurs in the head and at a location 1/3 of the way up the body from the tail compared to the un-exposed control. In contrast, a higher amount of Cu was detected in other portion of worm body, especially in its excretory cells and intestine when exposed to Cu2+. The results compared well with total Cu levels in nematodes, which were 4.10 ± 0.54, 12.32 ± 0.49 and 5.22 ± 0.63 μg g−1 dry weight for the PBS, Cu2+ and Cu nanoparticle groups, respectively, measured by ICP-MS. The nondestructive and multi-elemental μ-SRXRF provides an important tool for mapping the elemental distribution in the whole body of a single tiny nematode at lower levels.
Co-reporter:Yu-Feng Li, Chunying Chen, Bai Li, Qing Wang, Jiangxue Wang, Yuxi Gao, Yuliang Zhao and Zhifang Chai
Journal of Analytical Atomic Spectrometry 2007 - vol. 22(Issue 8) pp:NaN930-930
Publication Date(Web):2007/06/26
DOI:10.1039/B703310A
The present study was carried out to establish a method for simultaneous speciation analysis of selenium and mercury. Batch-wise elution using two different mobile phases that are suitable for selenium and mercury speciation leads to successful determination of both selenium and mercury standards in 30 minutes with good efficiency and resolution. The detection limits are in the range of 0.05–0.3 μg L−1 for selenium species, except TMSe, which has a poorer detection limit (1.48 μg L−1), and 2.5 μg L−1 for inorganic mercury (Hg2+) and 2.0 μg L−1 for organic mercury (CH3Hg+). The method was applied to analysis of urine samples from people who were long-term mercury exposed and supplemented with selenium-enriched yeast for 90 days. Selenocystine (SeCys) was found to be a major selenium form, while inorganic mercury is the major mercury form. The recoveries of spiked species were between 93 and 117% in all cases. The increased mercury concentrations in urine after 90-day selenium supplementation suggest that selenium is beneficial to the excretion of mercury from urine. The proposed technique may help to increase our understanding of the in vivo interaction between selenium and mercury in human body.
Co-reporter:Yu-Feng Li, Liang Hu, Bai Li, Xiaohan Huang, Erik H. Larsen, Yuxi Gao, Zhifang Chai and Chunying Chen
Journal of Analytical Atomic Spectrometry 2011 - vol. 26(Issue 1) pp:NaN229-229
Publication Date(Web):2010/11/25
DOI:10.1039/C0JA00129E
Accurate determination of selenium (Se) species in biological samples is a critical issue because Se commonly occurs at low levels and in diverse species. The method for the full quantification of Se species in serum samples was proposed through combined ion-pair reverse-phase (RP) chromatography and affinity chromatography (AF) hyphenated to inductively coupled plasma-(quadrupole) mass spectrometry (ICP-qMS) with post-column isotope dilution analysis (IDA) and a collision cell technique (CCT). Different Se species like inorganic Se (Se4+ and Se6+), selenocystine (SeCys), selenomethionine (SeMet), selenoprotein P (SelP), selenoalbumin (SeAlb) and glutathione peroxidase (GPx) can be separated and quantified. The proposed methodology was used to qualitatively and quantitatively study the dynamic distribution of Se species in human serum samples from the Hg-contaminated area after supplementation with 100 μg of Se daily as Se-enriched yeast for 180 days. SelP takes up almost half and even more of the total Se and increases with the Se administration. The repeatability in terms of relative standard deviation (R.S.D. %, n = 10) is 6% for GPx and SelP and 5% for SeAlb. The detection limits are 0.1 μg Se L−1 for GPx and other non-retained Se compounds, 1.0 μg Se L−1 for SelP and 1.2 μg Se L−1 for SeAlb, 1.3 μg Se L−1 for inorganic Se; 1.2 μg Se L−1 for SeCys; 1.1 μg Se L−1 for SeMet, respectively.
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