Co-reporter:Saijie Song, He Shen, Tao Yang, Lina Wang, Han Fu, Huabing Chen, and Zhijun Zhang
ACS Applied Materials & Interfaces March 22, 2017 Volume 9(Issue 11) pp:9484-9484
Publication Date(Web):March 3, 2017
DOI:10.1021/acsami.7b00490
Malignant tumor incidences have been rapidly rising recently and are becoming a serious threat to human health. Herein, a multifunctional cancer targeted theranostic nanoplatform is developed by in situ growth of iron oxide magnetic nanoparticles on carbon nanoparticles, and then loaded with fluorescent dye indocyanine green (ICG@MCNPs). The loading of ICG on the nanoplatform significantly improves its photostability, and hence facilitates long-term near-infrared fluorescence (NIRF) imaging and efficient photothermal therapy (PTT) of tumor. The in vivo NIRF imaging reveals that ICG@MCNPs can be targeted to the tumor site. Moreover, in vivo magnetic resonance imaging also confirmed the efficient accumulation of ICG@MCNPs in the tumor site. Inspiringly, the subsequent PTT of tumor-bearing mice is achieved, as evidenced by the complete ablation of the tumor and the recovery of the physiological indexes to normal levels. Benefitting from its low-cost, simple preparation, and excellent dual-modal imaging and therapy, the ICG@MCNPs-based theranostic nanoplatform holds great promise in tumor-targeted nanomedicine.Keywords: dual-modal imaging; indocyanine green; magnetic carbon nanoparticles; photothermal therapy; theranostic nanoplatform;
Co-reporter:Xiaoyun Liu, He Shen, Saijie Song, Wei Chen, Zhijun Zhang
Colloids and Surfaces B: Biointerfaces 2017 Volume 159(Volume 159) pp:
Publication Date(Web):1 November 2017
DOI:10.1016/j.colsurfb.2017.07.078
•GO-CA nanofibrous scaffolds with ECM mimicking structure to regulate hMSCs growth.•Incorporation of the GO for accelerated biomineralization.•Biomineralized GO-CA scaffolds on inducing osteogenic differentiation of hMSCs.For bone tissue engineering, it requires that the scaffolds have excellent biocompatibility, proper mechanical and osteoinductive properties. Electrospun nanofibers with extracellular matrices mimicking structure have proven to be good scaffolds for bone tissue repairing. Hybrid nanofibers in particular, endow the nanofibers with specific and multiple functionalities, and therefore have attracted increasing interests in the recent years. In this study, we fabricated graphene oxide (GO)-incorporated cellulose acetate (CA) nanofibrous scaffolds by electrospinning technique for enhancement of biomineralization and osteogenic differentiation of human mesenchymal stem cells (hMSCs). The results displayed the average fiber diameter was decreased from 595 to 285 nm with the presence of GO from 0 to 1 wt%. Furthermore, with incorporation of GO, the Young’s modulus of the nanofibers increased in a dose-dependent manner. More importantly, the incorporation of GO led to significantly enhanced adhesion and proliferation of hMSCs on the scaffolds, mainly due to the good biocompatibility and extracellular matrices mimicking structure of the hybrid nanofibers. Exposure of the nanofibers to the simulated body fluid revealed that the biomineralization was improved significantly with the doping of GO in the nanofibers, possibly owing to the more nucleation sites for calcium phosphate provided by GO. The accelerated biomineralization on the GO-CA nanofibers resulted in a markedly increase in the activity of biomineralization-relevant alkaline phosphatase, and thus induced osteogenic differentiation of hMSCs. The current work demonstrated that the GO-CA nanofibrous scaffolds may find potential applications in bone tissue engineering and other regenerative medicine fields.Incorporation of graphene oxide into cellulose acetate nanofibrous scaffolds resulted in enhanced biomineralization and osteogenic differentiation of mesenchymal stem cells.Download high-res image (183KB)Download full-size image
Co-reporter:Xiaolong Tu, Lina Wang, Yuhua Cao, Yufei Ma, He Shen, Mengxin Zhang, Zhijun Zhang
Carbon 2016 Volume 97() pp:35-44
Publication Date(Web):February 2016
DOI:10.1016/j.carbon.2015.05.043
The combination of different treatments in cancer therapy has drawn massive attention in the last decades due to its superior anticancer ability to single treatment. One of the most useful strategies to achieve this purpose is to design and construct efficient multifunctional nanoplatforms. Here we report our effort in development of carbon nanoparticles/doxorubicin@SiO2 nanocomposites and their application for combined photothermal and chemo-therapy in cancer ablation. The nanocomposites are obtained via reverse microemulsion method with controlled size and high drug loading ratio. These nanocomposites possess high heat-generating ability, pH responsive drug delivery, and heat-induced high drug release as well. In vitro experiment reveals that the combined photothermal and chemo-therapy exhibits much higher toxicity to 4T1 cells than photothermal therapy or chemotherapy alone. In vivo experiment reveals that compared with single treatment, the combined photothermal and chemo-therapy can effectively inhibit tumor growth and destroy it eventually without cancer recurrence. The current research demonstrates that carbon nanoparticles/doxorubicin@SiO2 nanocomposites can be used as an efficient nanoplatform for combined cancer photothermal and chemo-therapy.
Co-reporter:Jie Huang;Miao Guo;Hengte Ke;Cheng Zong;Bin Ren;Gang Liu;He Shen;Yufei Ma;Xiaoyong Wang;Hailu Zhang;Zongwu Deng;Huabing Chen
Advanced Materials 2015 Volume 27( Issue 34) pp:5049-5056
Publication Date(Web):
DOI:10.1002/adma.201501942
Co-reporter:Miao Guo;Jie Huang;Yibin Deng;He Shen;Yufei Ma;Mengxin Zhang;Aijun Zhu;Yanli Li;He Hui;Yangyun Wang;Xiangliang Yang;Huabing Chen
Advanced Functional Materials 2015 Volume 25( Issue 1) pp:59-67
Publication Date(Web):
DOI:10.1002/adfm.201402762
Stimuli-responsive anticancer agents are of particular interest in the field of cancer therapy. Nevertheless, so far stimuli-responsive photothermal agents have been explored with limited success for cancer photothermal therapy (PTT). In this work, as a proof-of-concept, a pH-responsive photothermal nanoconjugate for enhanced PTT efficacy, in which graphene oxide (GO) with broad NIR absorbance and effective photothermal conversion efficiency is selected as a typical model receptor of fluorescence resonance energy transfer (FRET), and grafted cyanine dye (e.g., Cypate) acts as the donor of near-infrared fluorescence (NIRF), is reported for the first time. The conjugate of Cypate-grafted GO exhibits different conformations in aqueous solutions at various pH, which can trigger pH-dependent FRET effect between GO and Cypate and thus induce pH-responsive photothermal effect of GO-Cypate. GO-Cypate exhibits severe cell damage owing to the enhanced photothermal effect in lysosomes, and thus generate synergistic PTT efficacy with tumor ablation upon photoirradiation after a single-dose intravenous injection. The photothermal nanoconjugate with broad NIR absorbance as the effective receptor of FRET can smartly convert emitted NIRF energy from donor cyanine dye into additional photothermal effect for improving PTT. These results suggest that the smart nanoconjugate can act as a promising stimuli-responsive photothermal nanoplatform for cancer therapy.
Co-reporter:Mengxin Zhang, Yuhua Cao, Lina Wang, Yufei Ma, Xiaolong Tu, and Zhijun Zhang
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 8) pp:4650
Publication Date(Web):February 12, 2015
DOI:10.1021/am5080453
Photothermal therapy (PTT) is a noninvasive and convenient way to ablate tumor tissues. Integrating PTT with imaging technique could precisely identify the location and the size of tumor regions, thereby significantly improving the therapeutic efficacy. Magnetic resonance imaging (MRI) is widely used in clinical diagnosis due to its superb spatial resolution and real-time monitoring feature. In our work, we developed a theranostic nanoplatform based on manganese doped iron oxide (MnIO) nanoparticles modified with denatured bovine serum albumin (MnIO-dBSA). The in vitro experiment revealed that the MnIO nanoparticles exhibited T1-weighted MRI capability (r1 = 8.24 mM–1 s–1, r2/r1 = 2.18) and good photothermal effect under near-infrared laser irradiation (808 nm). Using 4T1 tumor-bearing mice as an animal model, we further demonstrated that the MnIO-dBSA composites could significantly increase T1 MRI signal intensity at the tumor site (about two times) and effectively ablate tumor tissues with photoirradiation. Taken together, this work demonstrates the great potential of the MnIO nanoparticles as an ideal theranostic platform for efficient tumor MR imaging and photothermal therapy.Keywords: magnetic nanoparticles; MR imaging; photothermal therapy; theranostics
Co-reporter:Yu Luo, He Shen, Yongxiang Fang, Yuhua Cao, Jie Huang, Mengxin Zhang, Jianwu Dai, Xiangyang Shi, and Zhijun Zhang
ACS Applied Materials & Interfaces 2015 Volume 7(Issue 11) pp:6331
Publication Date(Web):March 5, 2015
DOI:10.1021/acsami.5b00862
Currently, combining biomaterial scaffolds with living stem cells for tissue regeneration is a main approach for tissue engineering. Mesenchymal stem cells (MSCs) are promising candidates for musculoskeletal tissue repair through differentiating into specific tissues, such as bone, muscle, and cartilage. Thus, successfully directing the fate of MSCs through factors and inducers would improve regeneration efficiency. Here, we report the fabrication of graphene oxide (GO)-doped poly(lactic-co-glycolic acid) (PLGA) nanofiber scaffolds via electrospinning technique for the enhancement of osteogenic differentiation of MSCs. GO-PLGA nanofibrous mats with three-dimensional porous structure and smooth surface can be readily produced via an electrospinning technique. GO plays two roles in the nanofibrous mats: first, it enhances the hydrophilic performance, and protein- and inducer-adsorption ability of the nanofibers. Second, the incorporated GO accelerates the human MSCs (hMSCs) adhesion and proliferation versus pure PLGA nanofiber and induces the osteogenic differentiation. The incorporating GO scaffold materials may find applications in tissue engineering and other fields.Keywords: electrospinning; graphene oxide; mesenchymal stem cells; nanofibrous mat; osteogenic differentiation; tissue engineering
Co-reporter:Saijie Song, Yufei Ma, He Shen, Mengxin Zhang and Zhijun Zhang
RSC Advances 2015 vol. 5(Issue 35) pp:27922-27932
Publication Date(Web):13 Mar 2015
DOI:10.1039/C4RA16982D
Dye-containing wastewater is one of the major issues in water contamination, and its treatment remains a serious problem due to the low concentrations of dyes in polluted natural water and high cost for purification. Herein, we report the application of graphene oxides (GO) in the decontamination of ppm levels of methylene blue (MB) in an aqueous solution. During the dye removal process, GO adsorbs MB molecules via strong interactions including π–π stacking and electrostatic attraction, and facilitates the precipitation of GO/MB complexes, which can be readily removed from the solution. The adsorption progress follows the Langmuir isotherm model and the pseudo-second-order kinetic model. The thermodynamic parameters indicate that the adsorption progress is a spontaneous progress. By using our strategy, a dye removal rate as high as 95% has been achieved with a final dye concentration of only 0.25 ppm. In addition, 82% of the dye can be recycled through ethanol extraction from the collected GO/MB complexes. All the results demonstrate that GO nanosheets can effectively remove and recover ppm levels of cationic dye pollutants, represented by MB, showing the promising application of GO in ultra-low concentration dye containing wastewater treatment.
Co-reporter:He Shen, Yufei Ma, Yu Luo, Xiaoyun Liu, Zhijun Zhang, Jianwu Dai
Colloids and Surfaces B: Biointerfaces 2015 Volume 135() pp:332-338
Publication Date(Web):1 November 2015
DOI:10.1016/j.colsurfb.2015.07.062
•Preparation of MC scaffolds with three-dimensional porous structure for regulating the fate of MSCs.•Direction osteogenic differentiation of MSCs via MC scaffolds.•Stimulatory effect of mechanical properties and 3D structure of the MC scaffolds on inducing the stem cell differentiation without osteogenic inducer supplement.Development of three-dimensional (3D) biodegradable scaffolds that can accelerate mesenchymal stem cell (MSC) osteogenic differentiation is a decisive prerequisite for treatment of damaged skeletal tissue. We report herein the preparation of methylcellulose-based (MC) scaffolds using carbonyldiimidazole as cross-linking agent to produce substrates with specific cross-linking density and porous structure, as well as their applications for directing hMSC toward osteoblasts. The mechanical properties of the scaffolds were controlled by cross-linking density. Human MSCs (hMSCs) seeded on the MC scaffolds have penetrated into the pores, and showed high viability (>80%) as revealed by WST assay and Live/Dead assay. Moreover, the results of differentiation experiments indicated that hMSCs cultured on MC substrates displayed high level of osteogenic differentiation marker expression, alkaline phosphatase activity and osteocalcin secretion, suggesting that the MC scaffolds can direct hMSC differentiation toward osteoblasts without inducer treatment and cross-linking density of MC scaffolds have stimulatory effect on inducing differentiation. The 3D MC scaffolds could be applicable as promising scaffolds for bone tissue repair.
Co-reporter:Yuhua Cao;Yufei Ma;Mengxin Zhang;Haiming Wang;Xiaolong Tu;He Shen;Jianwu Dai;Huichen Guo
Advanced Functional Materials 2014 Volume 24( Issue 44) pp:6963-6971
Publication Date(Web):
DOI:10.1002/adfm.201401358
Adjuvants play an important role in vaccines. Alum and MF59 are two dominant kinds of adjuvants used in humans. Both of them, however, have limited capacity to generate the cellular immune response required for vaccines against cancers and viral diseases. It is desirable to develop new and efficient adjuvants with the aim of improving the cellular immune response against the antigen. Here, the feasibility and efficiency of ultrasmall graphene oxide supported gold nanoparticles (usGO-Au) as a new immune adjuvant to improve immune responses are explored. usGO-Au is obtained from reduction of chloroauric acid using usGO and then decorated with ovalbumin (OVA, a model antigen) through physical adsorption to construct usGO-Au@OVA. As the results show, the as-synthesized usGO-Au@OVA can efficiently stimulate RAW264.7 cells to secrete tumor necrosis factor-α (TNF-α), a mediator for cellular immune response. In vivo studies demonstrate that usGO-Au@OVA can also promote robust OVA specific antibody response, CD8+ T cells proliferation, and different cytokines secretion. The results indicate that using usGO-Au as an adjuvant can stimulate potent humoral and cellular immune responses against antigens, which may promote better understanding of cellular immune response and facilitate potential applications for cancer and viral vaccines.
Co-reporter:Xiaolong Tu, Yufei Ma, Yuhua Cao, Jie Huang, Mengxin Zhang and Zhijun Zhang
Journal of Materials Chemistry A 2014 vol. 2(Issue 15) pp:2184-2192
Publication Date(Web):31 Jan 2014
DOI:10.1039/C3TB21750G
Photothermal therapy (PTT) is an emerging technique for effective cancer elimination in animal experiments. The key to the success of the PTT is to develop efficient and safe photosensitive agents. Activated carbon (AC), a widespread material safely used in routine and emergent medical services, is emerging as a nascent PTT agent. Here we report for the first time synthesis and in vitro PTT application of carbon nanoparticles (CNPs, less than 10 nm) derived from AC. In our strategy, CNPs are obtained via chemical oxidation and transferred to PEGylated CNPs (PCNPs) to reduce nonspecific adsorption and to improve biocompatibility. Fluorescein isothiocyanate is conjugated to PCNPs to examine time-dependent uptake by human breast cancer cells (MCF-7). The photothermal effect experiment demonstrates that PCNPs possess much stronger photothermal conversion ability than carbon dots (CDs). In the dark, PCNPs pose negligible threats to cell viability and membrane integrity, while upon near infrared (NIR) irradiation PCNPs can effectively kill cancer cells. The current work demonstrates that PCNPs can be used as an efficient and safe PTT agent.
Co-reporter:Yu Chong, Yufei Ma, He Shen, Xiaolong Tu, Xuan Zhou, Jiaying Xu, Jianwu Dai, Saijun Fan, Zhijun Zhang
Biomaterials 2014 35(19) pp: 5041-5048
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.03.021
Co-reporter:Jie Huang, Cheng Zong, He Shen, Yuhua Cao, Bin Ren and Zhijun Zhang
Nanoscale 2013 vol. 5(Issue 21) pp:10591-10598
Publication Date(Web):29 Aug 2013
DOI:10.1039/C3NR03264G
We have developed a graphene oxide (GO)-based nanoplatform simultaneously loaded with a chemical drug and Ag nanoparticles (NPs), and employed it to study the drug release from GO in living cells by surface-enhanced Raman spectroscopy (SERS). In our strategy, doxorubicin (DOX), a typical model anticancer drug, was loaded onto chemically prepared GO by means of π–π stacking, while the AgNPs were covalently modified onto GO. After incubation of the DOX- and AgNPs-loaded GO with Ca Ski cells for several hours, DOX will detach from the GO in an acidic environment due to the pH-dependent π–π interaction between DOX and GO. Real-time measurement of SERS signals of DOX using the GO loaded with AgNPs as a SERS-active substrate allows us to monitor the process of the drug release inside the living cell. The SERS results reveal that DOX is initially released from the GO surface inside the lysosomes, then escapes into the cytoplasm, and finally enters the nucleus, while GO, the nanocarrier, remains within the cytoplasm, without entering the nucleus.
Co-reporter:Yuhua Cao, Yu Chong, He Shen, Mengxin Zhang, Jie Huang, Yimin Zhu and Zhijun Zhang
Journal of Materials Chemistry A 2013 vol. 1(Issue 41) pp:5602-5610
Publication Date(Web):22 Aug 2013
DOI:10.1039/C3TB20764A
The PI3K–AKT–mTOR pathway plays an important role in tumor cell growth, invasion, migration and apoptosis. A blockade of this signaling pathway has arisen as a compelling target for the tumor therapy. However, there is cross-talking between different signal pathways. Combined treatment of tumors with different signal pathway inhibitors is considered as an efficient strategy for cancer therapy. NVP-BEZ235 is a dual pan-class I PI3K and mTOR kinase inhibitor currently in clinical trial. TNF-α is involved in the regulation of cell apoptosis. In the current work, we explored the combined use of BEZ235 and TNF-α on the PIK3CA mutant colorectal cancer (CRC) cell proliferation inhibition. In our strategy, the BEZ235 is loaded on PEGylated graphene oxide (GO-PEG) by physisorption via π–π stacking to enhance its aqueous solubility. The resulting GO-BEZ235 complex exhibited excellent aqueous solubility while retaining a high cancer cell killing potency. The combination of BEZ235 and TNF-α shows an enhanced cellular proliferation inhibition for HCT 116 through enhancing the G1 phase arrest and cell apoptosis compared to either drug alone. Moreover, our experiments reveal that the enhanced tumor cell apoptosis depends on the activation of caspase-9, caspase-8 and caspase-3 mediated by the increased phosphorylation level of JNK. Taken together, our findings demonstrate for the first time the feasibility of BEZ235 delivered by GO-PEG and of the combined use of BEZ235 and TNF-α for PIK3CA mutant CRC therapy.
Co-reporter:Liming Zhang, Zunliang Wang, Zhuoxuan Lu, He Shen, Jie Huang, Qinghuan Zhao, Min Liu, Nongyue He and Zhijun Zhang
Journal of Materials Chemistry A 2013 vol. 1(Issue 6) pp:749-755
Publication Date(Web):20 Nov 2012
DOI:10.1039/C2TB00096B
Single stranded ribonucleic acid (ssRNA) acts as a probe, antisense (AS), miRNA analog and inhibitor, and is promising for gene therapy and molecular diagnosis. However, free ssRNA exhibits poor cellular uptake due to its negative charges, and enzyme instability, which have largely limited the practical applications of ssRNA in biomedicine. To address these issues, we have developed a PEGylated reduced graphene oxide (PEG–RGO) nanovector for efficient delivery of ssRNA. We have demonstrated that PEG–RGO exhibits superior ssRNA loading and delivery capability, compared to the widely studied PEGylated graphene oxide (PEG–GO). Computational simulation further suggested that PEG–RGO binds ssRNA much stronger than PEG–GO, consistent with the experimental results. These results will have implications in designing RGO-based biocompatible and efficient ssRNA delivery systems.
Co-reporter:Guodong Liu, He Shen, Jinning Mao, Liming Zhang, Zhen Jiang, Tao Sun, Qing Lan, and Zhijun Zhang
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 15) pp:6909
Publication Date(Web):July 12, 2013
DOI:10.1021/am402128s
Transferrin (Tf), an iron-transporting serum glycoprotein that binds to receptors overexpressed at the surface of glioma cells, was chosen as the ligand to develop Tf-conjugated PEGylated nanoscaled graphene oxide (GO) for loading and glioma targeting delivery of anticancer drug doxorubicin (Dox) (Tf-PEG-GO-Dox). Tf-GO with lateral dimensions of 100–400 nm exhibited a Dox loading ratio up to 115.4%. Compared with Dox-loaded PEGylated GO (PEG-GO-Dox) and free Dox, Tf-PEG-GO-Dox displayed greater intracellular delivery efficiency and stronger cytotoxicity against C6 glioma cells. A competition test showed that Tf was essential to glioma targeting in vitro. The HPLC assay for Dox concentration in tumor tissue and contrapart tissue of the brain demonstrated that Tf-PEG-GO-Dox could deliver more Dox into tumor in vivo. The life span of tumor bearing rats after the administration of Tf-PEG-GO-Dox was extended significantly compared to the rats treated with saline, Dox, and PEG-GO-Dox. In conclusion, we developed Tf-PEG-GO-Dox which exhibited significantly improved therapeutic efficacy for glioma both in vitro and in vivo.Keywords: chemotherapy; doxorubicin; glioma; graphene oxide; in vivo; transferrin;
Co-reporter:Mengxin Zhang, Yuhua Cao, Yu Chong, Yufei Ma, Hailu Zhang, Zongwu Deng, Chunhong Hu, and Zhijun Zhang
ACS Applied Materials & Interfaces 2013 Volume 5(Issue 24) pp:13325
Publication Date(Web):December 6, 2013
DOI:10.1021/am404292e
Magnetic resonance imaging (MRI) is a powerful and widely used clinical technique in cancer diagnosis. MRI contrast agents (CAs) are often used to improve the quality of MRI-based diagnosis. In this work, we developed a positive T1 MRI CA based on graphene oxide (GO)–gadolinium (Gd) complexes. In our strategy, diethylenetriaminepentaacetic acid (DTPA) is chemically conjugated to GO, followed by Gd(III) complexation, to form a T1 MRI CA (GO–DTPA–Gd). We have demonstrated that the GO–DTPA–Gd system significantly improves MRI T1 relaxivity and leads to a better cellular MRI contrast effect than Magnevist, a commercially used CA. Next, an anticancer drug, doxorubicin (DOX), was loaded on the surface of GO sheets via physisorption. Thus-prepared GO–DTPA–Gd/DOX shows significant cytotoxicity to the cancer cells (HepG2). This work provides a novel strategy to build a GO-based theranostic nanoplatform with T1-weighted MRI, fluorescence imaging, and drug delivery functionalities.Keywords: cellular imaging; contrast agents; graphene oxide; MR imaging; theranostics;
Co-reporter:He Shen, Min Liu, Yu Chong, Jie Huang and Zhijun Zhang
Toxicology Research 2013 vol. 2(Issue 6) pp:379-387
Publication Date(Web):11 Sep 2013
DOI:10.1039/C3TX50074H
A hydrolytically degradable poly(amino ester) is synthesized and evaluated as a protein delivery vector in vitro. The poly(amino ester), with cleavable ester bonds, can degrade into nontoxic products both in vitro and in vivo under physiological conditions, exhibiting low toxicity. Our experiments reveal that the poly(amino ester) can efficiently condense proteins via electrostatic interaction, and is significantly less toxic than PEI 25 kDa. Using fluorescein isothiocyanate (FITC) labeled bovine serum albumin and ribonuclease A as model proteins, the degradable poly(amino ester) can efficiently deliver proteins into cells and regulate cell functions. These results suggest that the degradable poly(amino ester) is a promising and efficient protein delivery vector.
Co-reporter:He Shen, Min Liu, Huixin He, Liming Zhang, Jie Huang, Yu Chong, Jianwu Dai, and Zhijun Zhang
ACS Applied Materials & Interfaces 2012 Volume 4(Issue 11) pp:6317
Publication Date(Web):October 30, 2012
DOI:10.1021/am3019367
Delivery of proteins into cells may alter cellular functions as various proteins are involved in cellular signaling by activating or deactivating the corresponding pathways and, therefore, can be used in cancer therapy. In this study, we have demonstrated for the first time that PEGylated graphene oxide (GO) can be exploited as a nanovector for efficient delivery of proteins into cells. In this approach, GO was functionalized with amine-terminated 6-armed polyethylene glycol (PEG) molecules, thereby providing GO with proper physiological stability and biocompatibility. Proteins were then loaded onto PEG-grafted GO (GO-PEG) with high payload via noncovalent interactions. GO-PEG could deliver proteins to cytoplasm efficiently, protecting them from enzymatic hydrolysis. The protein delivered by GO-PEG reserves its biological activity that regulates the cell fate. As a result, delivery of ribonuclease A (RNase A) led to cell death and transport of protein kinase A (PKA) induced cell growth. Taken together, this work demonstrated the feasibility of PEGlyated GO as a promising protein delivery vector with high biocompatibility, high payload capacity and, more importantly, capabilities of protecting proteins from enzymatic hydrolysis and retaining their biological functions.Keywords: cellular uptake; enzymatic hydrolysis; graphene oxide; loading capacity; protein delivery; regulation of cell function;
Co-reporter:Weihong Chen, Yuhua Cao, Min Liu, Qinghuan Zhao, Jie Huang, Hailu Zhang, Zongwu Deng, Jianwu Dai, David F. Williams, Zhijun Zhang
Biomaterials 2012 33(31) pp: 7895-7902
Publication Date(Web):
DOI:10.1016/j.biomaterials.2012.07.016
Co-reporter:Yi Zhang, Biao Chen, Liming Zhang, Jie Huang, Fenghua Chen, Zupei Yang, Jianlin Yao and Zhijun Zhang
Nanoscale 2011 vol. 3(Issue 4) pp:1446-1450
Publication Date(Web):07 Feb 2011
DOI:10.1039/C0NR00776E
We describe a facile approach to controllable assembly of monodisperse Fe3O4 nanoparticles (NPs) on chemically reduced graphene oxide (rGO). First, reduction and functionalization of GO by polyetheylenimine (PEI) were achieved simultaneously by simply heating the PEI and GO mixture at 60 °C for 12 h. The process is environmentally friendly and convenient compared with previously reported methods. Meso-2,3-dimercaptosuccinnic acid (DMSA)-modified Fe3O4 NPs were then conjugated to the PEI moiety which is located on the periphery of the GO sheets via formation of amide bonds between COOH groups of DMSA molecules bound on the surface of the Fe3O4 NPs and amine groups of PEI. The magnetic GO composites were characterized by means of TEM, AFM, UV-vis, FTIR, Raman, TGA, and VSM measurements. Finally, preliminary results of using the Fe3O4-rGO composites for efficient removal of tetracycline, an antibiotic that is often found as a contaminant in the environment, are reported.
Co-reporter:Biao Chen, Min Liu, Liming Zhang, Jie Huang, Jianlin Yao and Zhijun Zhang
Journal of Materials Chemistry A 2011 vol. 21(Issue 21) pp:7736-7741
Publication Date(Web):13 Apr 2011
DOI:10.1039/C1JM10341E
A novel gene delivery system based on graphene oxide chemically-functionalized with branched polyethylenimine (PEI-GO) is reported. The PEI-GO conjugate was formed by the covalent linking of PEI and GO via an amide bond by widely used EDC chemistry. Thus-prepared PEI-GO exhibits an excellent ability to condense DNA at a low mass ratio with a positive potential of 49 mV. A WST assay reveals that PEI-GO is significantly less cytotoxic than PEI 25 kDa. Finally, the transfection efficiency of PEI-GO was evaluated. It is demonstrated that the luciferase expression of PEI-GO is comparable or even higher than that of the PEI 25 kDa at optimal mass ratio. Moreover, intracellular tracking of Cy3-labelled pGL-3 indicates that PEI-GO could effectively deliver plasmid DNA into cells and be localized in the nucleus. These findings suggest that PEI-GO is a promising candidate for efficient gene delivery.
Co-reporter:Weihong Chen, Peiwei Yi, Yi Zhang, Liming Zhang, Zongwu Deng, and Zhijun Zhang
ACS Applied Materials & Interfaces 2011 Volume 3(Issue 10) pp:4085
Publication Date(Web):September 1, 2011
DOI:10.1021/am2009647
Formation of composites of dextran-coated Fe3O4 nanoparticles (NPs) and graphene oxide (Fe3O4-GO) and their application as T2-weighted contrast agent for efficient cellular magnetic resonance imaging (MRI) are reported. Aminodextran (AMD) was first synthesized by coupling reaction of carboxymethyldextran with butanediamine, which was then chemically conjugated to meso-2,3-dimercaptosuccinnic acid-modified Fe3O4 NPs. Next, the AMD-coated Fe3O4 NPs were anchored onto GO sheets via formation of amide bond in the presence of 1-ethyl-3-(3-dimethyaminopropyl) carbodiimide (EDC). It is found that the Fe3O4-GO composites possess good physiological stability and low cytotoxicity. Prussian Blue staining analysis indicates that the Fe3O4-GO nanocomposites can be internalized efficiently by HeLa cells, depending on the concentration of the composites incubated with the cells. Furthermore, compared with the isolated Fe3O4 NPs, the Fe3O4-GO composites show significantly enhanced cellular MRI, being capable of detecting cells at the iron concentration of 5 μg mL–1 with cell density of 2 × 105 cells mL–1, and at the iron concentration of 20 μg mL–1 with cell density of 1000 cells mL–1.Keywords: cell labeling; composites; Fe3O4 nanoparticles; graphene oxide; MRI;
Co-reporter:Min Liu, Biao Chen, Yanan Xue, Jie Huang, Liming Zhang, Shiwen Huang, Qingwen Li, and Zhijun Zhang
Bioconjugate Chemistry 2011 Volume 22(Issue 11) pp:2237
Publication Date(Web):October 13, 2011
DOI:10.1021/bc200189f
Functionalized multiwalled carbon nanotubes (f-MWNTs) are of great interest and designed as a novel gene delivery system. In this paper, we presented synthesis of polyamidoamine-functionalized multiwalled carbon nanotubes (PAA-g-MWNTs) and their application as a novel gene delivery system. The PAA-g-MWNTs, obtained from amide formation between PAA and chemically oxidized MWNTs, were stable in aqueous solution and much less toxic to cells than PAA and PEI 25KDa. More importantly, PAA-g-MWNTs showed comparable or even higher transfection efficiency than PAA and PEI at optimal w/w ratio. Intracellular trafficking of Cy3-labeled pGL-3 indicated that a large number of Cy3-labeled pGL-3 were attached to nucleus membrane, the majority of which was localized in nucleus after incubation with cells for 24 h. We have demonstrated that PAA modification of MWNTs facilitate higher DNA uptake and gene expression in vitro. All these facts suggest potential application of PAA-g-MWNTs as a novel gene vector with high transfection efficiency and low cytotoxicity.
Co-reporter:Qinghuan Zhao, Weihong Chen, Yuanding Chen, Liming Zhang, Jinping Zhang, and Zhijun Zhang
Bioconjugate Chemistry 2011 Volume 22(Issue 3) pp:346
Publication Date(Web):February 21, 2011
DOI:10.1021/bc1002532
Proteins of viral capsid may self-assemble into virus-like particles (VLPs) that can find many biomedical applications such as platform for drug delivery. In this paper, we describe preparation of VLPs by self-assembly of VP6, a rotavirus capsid protein that was chemically conjugated with doxorubicin (DOX), an anticancer drug. VP6 was first highly expressed in E. Coli, followed by purification and renaturation. DOX was then covalently attached to VP6 to form DOX-VP6 (DVP6) conjugates, which were subsequently self-assembled into VLPs under appropriate condition. Next, lactobionic acid (LA) was chemically linked to the surface of the VLPs. We demonstrated that the aforementioned nanosystem shows specific targeting to hepatoma cell line HepG2. The chemically functionalized VLPs, a kind of biological nanoparticles with excellent biocompatibility and biodegradability, can be prepared in large scale from E. Coli through our method, which may find practical applications in biomedicine.
Co-reporter:Jie Huang, Liming Zhang, Biao Chen, Nan Ji, Fenghua Chen, Yi Zhang and Zhijun Zhang
Nanoscale 2010 vol. 2(Issue 12) pp:2733-2738
Publication Date(Web):11 Oct 2010
DOI:10.1039/C0NR00473A
In this paper, we describe the formation of Au nanoparticle-graphene oxide (Au-GO) and -reduced GO (Au-rGO) composites by noncovalent attachment of Au nanoparticles premodified with 2-mercaptopyridine to GO and rGO sheets, respectively, via π–π stacking and other molecular interactions. Compared with in situ reduction of HAuCl4 on the surface of graphene sheets that are widely used to prepare Au-GO composites, the approach developed by us offers well controlled size, size distribution, and morphology of the metal nanoparticles in the metal-GO nanohybrids. Moreover, we investigated surface enhanced Raman scattering (SERS) and catalysis properties of the Au-graphene composites. We have demonstrated that the Au-GO composites are superior SERS substrates to the Au NPs. Similarly, a comparative study on the catalytic activities of the Au, Au-GO, and Au-rGO composites in the reduction of o-nitroaniline to 1,2-benzenediamine by NaBH4 indicates that both Au-GO and Au-rGO composites exhibit significantly higher catalytic activities than the corresponding Au nanoparticles.
Co-reporter:Feng-Hua Chen, Li-Ming Zhang, Qing-Tao Chen, Yi Zhang and Zhi-Jun Zhang
Chemical Communications 2010 vol. 46(Issue 45) pp:8633-8635
Publication Date(Web):12 Oct 2010
DOI:10.1039/C0CC02577A
Coating a layer of PEG functionalized porous silica shell onto doxorubicin-conjugated Fe3O4 nanoparticles, we demonstrated, provides a number of combined advantages in view of the magnetic carrier's therapeutic functionality to treat tumors.
Co-reporter:Yuhua Cao, Yu Chong, He Shen, Mengxin Zhang, Jie Huang, Yimin Zhu and Zhijun Zhang
Journal of Materials Chemistry A 2013 - vol. 1(Issue 41) pp:NaN5610-5610
Publication Date(Web):2013/08/22
DOI:10.1039/C3TB20764A
The PI3K–AKT–mTOR pathway plays an important role in tumor cell growth, invasion, migration and apoptosis. A blockade of this signaling pathway has arisen as a compelling target for the tumor therapy. However, there is cross-talking between different signal pathways. Combined treatment of tumors with different signal pathway inhibitors is considered as an efficient strategy for cancer therapy. NVP-BEZ235 is a dual pan-class I PI3K and mTOR kinase inhibitor currently in clinical trial. TNF-α is involved in the regulation of cell apoptosis. In the current work, we explored the combined use of BEZ235 and TNF-α on the PIK3CA mutant colorectal cancer (CRC) cell proliferation inhibition. In our strategy, the BEZ235 is loaded on PEGylated graphene oxide (GO-PEG) by physisorption via π–π stacking to enhance its aqueous solubility. The resulting GO-BEZ235 complex exhibited excellent aqueous solubility while retaining a high cancer cell killing potency. The combination of BEZ235 and TNF-α shows an enhanced cellular proliferation inhibition for HCT 116 through enhancing the G1 phase arrest and cell apoptosis compared to either drug alone. Moreover, our experiments reveal that the enhanced tumor cell apoptosis depends on the activation of caspase-9, caspase-8 and caspase-3 mediated by the increased phosphorylation level of JNK. Taken together, our findings demonstrate for the first time the feasibility of BEZ235 delivered by GO-PEG and of the combined use of BEZ235 and TNF-α for PIK3CA mutant CRC therapy.
Co-reporter:Xiaolong Tu, Yufei Ma, Yuhua Cao, Jie Huang, Mengxin Zhang and Zhijun Zhang
Journal of Materials Chemistry A 2014 - vol. 2(Issue 15) pp:NaN2192-2192
Publication Date(Web):2014/01/31
DOI:10.1039/C3TB21750G
Photothermal therapy (PTT) is an emerging technique for effective cancer elimination in animal experiments. The key to the success of the PTT is to develop efficient and safe photosensitive agents. Activated carbon (AC), a widespread material safely used in routine and emergent medical services, is emerging as a nascent PTT agent. Here we report for the first time synthesis and in vitro PTT application of carbon nanoparticles (CNPs, less than 10 nm) derived from AC. In our strategy, CNPs are obtained via chemical oxidation and transferred to PEGylated CNPs (PCNPs) to reduce nonspecific adsorption and to improve biocompatibility. Fluorescein isothiocyanate is conjugated to PCNPs to examine time-dependent uptake by human breast cancer cells (MCF-7). The photothermal effect experiment demonstrates that PCNPs possess much stronger photothermal conversion ability than carbon dots (CDs). In the dark, PCNPs pose negligible threats to cell viability and membrane integrity, while upon near infrared (NIR) irradiation PCNPs can effectively kill cancer cells. The current work demonstrates that PCNPs can be used as an efficient and safe PTT agent.
Co-reporter:Liming Zhang, Zunliang Wang, Zhuoxuan Lu, He Shen, Jie Huang, Qinghuan Zhao, Min Liu, Nongyue He and Zhijun Zhang
Journal of Materials Chemistry A 2013 - vol. 1(Issue 6) pp:NaN755-755
Publication Date(Web):2012/11/20
DOI:10.1039/C2TB00096B
Single stranded ribonucleic acid (ssRNA) acts as a probe, antisense (AS), miRNA analog and inhibitor, and is promising for gene therapy and molecular diagnosis. However, free ssRNA exhibits poor cellular uptake due to its negative charges, and enzyme instability, which have largely limited the practical applications of ssRNA in biomedicine. To address these issues, we have developed a PEGylated reduced graphene oxide (PEG–RGO) nanovector for efficient delivery of ssRNA. We have demonstrated that PEG–RGO exhibits superior ssRNA loading and delivery capability, compared to the widely studied PEGylated graphene oxide (PEG–GO). Computational simulation further suggested that PEG–RGO binds ssRNA much stronger than PEG–GO, consistent with the experimental results. These results will have implications in designing RGO-based biocompatible and efficient ssRNA delivery systems.
Co-reporter:Feng-Hua Chen, Li-Ming Zhang, Qing-Tao Chen, Yi Zhang and Zhi-Jun Zhang
Chemical Communications 2010 - vol. 46(Issue 45) pp:NaN8635-8635
Publication Date(Web):2010/10/12
DOI:10.1039/C0CC02577A
Coating a layer of PEG functionalized porous silica shell onto doxorubicin-conjugated Fe3O4 nanoparticles, we demonstrated, provides a number of combined advantages in view of the magnetic carrier's therapeutic functionality to treat tumors.
Co-reporter:Biao Chen, Min Liu, Liming Zhang, Jie Huang, Jianlin Yao and Zhijun Zhang
Journal of Materials Chemistry A 2011 - vol. 21(Issue 21) pp:NaN7741-7741
Publication Date(Web):2011/04/13
DOI:10.1039/C1JM10341E
A novel gene delivery system based on graphene oxide chemically-functionalized with branched polyethylenimine (PEI-GO) is reported. The PEI-GO conjugate was formed by the covalent linking of PEI and GO via an amide bond by widely used EDC chemistry. Thus-prepared PEI-GO exhibits an excellent ability to condense DNA at a low mass ratio with a positive potential of 49 mV. A WST assay reveals that PEI-GO is significantly less cytotoxic than PEI 25 kDa. Finally, the transfection efficiency of PEI-GO was evaluated. It is demonstrated that the luciferase expression of PEI-GO is comparable or even higher than that of the PEI 25 kDa at optimal mass ratio. Moreover, intracellular tracking of Cy3-labelled pGL-3 indicates that PEI-GO could effectively deliver plasmid DNA into cells and be localized in the nucleus. These findings suggest that PEI-GO is a promising candidate for efficient gene delivery.
Co-reporter:Hao Chen, Lina Wang, Han Fu, Zhiying Wang, Yujie Xie, Zhijun Zhang and Yu Tang
Journal of Materials Chemistry A 2016 - vol. 4(Issue 46) pp:NaN7480-7480
Publication Date(Web):2016/10/27
DOI:10.1039/C6TB01422D
The development of multimodal nanoprobes is of great importance in nanomedicine because it integrates the advantages of each imaging modality and offers a significantly enhanced diagnostic effect. In this work, gadolinium(III) functionalized fluorescent carbon dots (Gd-CDs) are synthesized by means of a one-step hydrothermal approach. As a fluorescent nanomaterial, the obtained Gd-CDs exhibit strong and stable fluorescence with excitation-independent emission behavior. Moreover, as an MRI contrast agent, the Gd-CDs exhibited a longitudinal relaxation rate of 6.06 mM−1 s−1, which is significantly higher than that of the commercially available MRI agent Gadovist (4.24 mM−1 s−1). In addition, the cellular experiment reveals that Gd-CDs promote the proliferation of human mesenchymal stem cells (hMSCs), which is tracked by the fluorescence/Magnetic Resonance dual-modality imaging of hMSCs by the Gd-CDs.
