Co-reporter:Guoyong Zhou, Hong Xiao, Xiaoxia Li, Yi Huang, ... Xintao Shuai
Acta Biomaterialia 2017 Volume 64(Volume 64) pp:
Publication Date(Web):1 December 2017
DOI:10.1016/j.actbio.2017.10.018
A pH-sensitive copolymer PAsp(DIP)-b-PAsp(MEA) (PDPM) was synthesized and self-assembled to micelle loading chemotherapeutic drug doxorubicin (DOX) and introducing a gold nanocage structure for photothermo-chemotherapy and photoacoustic imaging. After further surface modification with polyethylene glycol (PEG), the DOX-loaded pH-sensitive gold nanocage (D-PGNC) around 100 nm possessed a uniform spherical structure with a pH-sensitive core of PAsp(DIP) incorporating DOX, an interlayer crosslinked via disulfide bonds and decorated with discontinuous gold shell, and a PEG corona. The release of DOX from D-PGNC was turned off in bloodstream due to the cross-linking and gold decoration of interlayer but turned on inside tumor tissue by multiple stimulations including the low pH value of tumor tissue (≈6.8), the low lysosomal pH value of cancer cells (≈5.0) and near-infrared (NIR) irradiation. The gold nanocage receiving NIR irradiation could generate hyperthermia to ablate tumor cells. Moreover, the photoacoustic (PA) imaging and analysis of DOX fluorescence inside tumor tissue demonstrated that photothermal therapy based on the gold nanocage effectively drove DOX penetration inside tumor. Owing to the rapid intratumor release and deep tissue penetration of drug favorable for killing cancer cells survived the photothermal therapy, the combined therapy based on D-PGNC via NIR irradiation exhibited a synergistic treatment effect superior to either chemotherapy or NIR-induced photothermal therapy alone.Statement of SignificanceThe novelty of the manuscript is its multifunctional system which incorporates anticancer drug DOX in its pH-sensitive core and acts as a template to introduce a gold nanocage. This nanomedicine presents potentials of sequestrating drug molecules in blood circulation but releasing them inside tumor upon responding to the acidic microenvironment therein. Exposure to NIR laser further expedited the pH-sensitive DOX release and promoted DOX penetration into cancer tissues far away from the vasculature. Consequently, the combined photothermo-chemotherapy showed synergistic effects to inhibit tumor growth and prolong animal survival in nude mice bearing human SKOV-3 ovarian tumor. Moreover, owing to the decoration with gold nanocage, the tumor accumulation and intratumor diffusion of the micelles were easily trackable using photoacoustic imaging.Download high-res image (239KB)Download full-size image
Co-reporter:Liteng Lin, Mingyue Cai, Shaohui Deng, Wensou Huang, Jingjun Huang, Xinghua Huang, Mingsheng Huang, Yong Wang, Xintao Shuai, Kangshun Zhu
Nanomedicine: Nanotechnology, Biology and Medicine 2017 Volume 13, Issue 7(Issue 7) pp:
Publication Date(Web):1 October 2017
DOI:10.1016/j.nano.2017.06.019
Portal hypertension (PH), a leading cause of mortality in cirrhosis, lacks effective clinical therapeutic strategies. The increased thromboxane A2 (TXA2), derived primarily from the upregulation of cyclooxygenase-1 (COX-1) in cirrhotic liver sinusoidal endothelial cells (LSECs), is responsible for hepatic endothelial dysfunction and PH. Thus, blocking the COX-1 pathway in cirrhotic LSECs may benefit the treatment of PH. In this study, hyaluronate-graft-polyethylenimine (HA-PEI) was synthesized for the targeted delivery of COX-1 siRNA to LSECs. Compared to non-targeted PEI, HA-PEI mediated much more efficient siRNA delivery, which resulted in potent targeted gene silencing in LSECs. In vivo, HA-PEI notably increased the accumulation of siRNA along the sinusoidal lining of the liver, inhibited over-activation of the COX-1/TXA2 pathway in LSECs, and successfully reduced portal pressure in cirrhotic mice. These results highlight the potential of HA-PEI complexed siRNA to serve as a LSECs-specific nanomedical system for effective gene therapy in PH.Hyaluronate-graft-polyethylenimine (HA-PEI) was synthesized for targeted delivery of cyclooxygenase-1 (COX-1) siRNA to liver sinusoidal endothelial cells (LSECs) for the treatment of portal hypertension in cirrhotic mice. In vivo, HA-PEI remarkably increased the efficiency of siRNA delivery to liver sinusoidal endothelium, inhibited the over-activation of COX-1 pathway in LSECs, and successfully reduced the portal pressure in cirrhotic mice.Download high-res image (169KB)Download full-size image
Co-reporter:Weitong Sun;Yong Wang;Mingyue Cai;Liteng Lin;Xiaoyan Chen;Zhong Cao;Kangshun Zhu;Xintao Shuai
Biomaterials Science (2013-Present) 2017 vol. 5(Issue 12) pp:2468-2479
Publication Date(Web):2017/11/21
DOI:10.1039/C7BM00866J
Hepatocellular carcinoma (HCC) is one of the most common malignancies imposing a serious threat to human health worldwide. To date, the effect of HCC chemotherapy has been limited due to drug resistance. Combination therapy of chemotherapeutic drugs and siRNA represents an emerging strategy that may improve anticancer effects by synergistic actions. The current study was aimed at achieving better HCC treatment via combination therapy, in which PEI-modified liposomes prepared by a thin-film hydration method were used to codeliver sorafenib (SF) and siRNA targeting GPC3 gene (siGPC3). Under optimized experimental conditions, SF and siGPC3 were effectively loaded into liposomes (SF-PL/siGPC3). SF-PL/siGPC3 with selected sizes and zeta potentials effectively accumulated at tumor sites and entered HCC cells. The two codelivered therapeutic agents exerted good anticancer effects by jointly suppressing the expression of the anti-apoptotic GPC3 gene and the proliferative cyclin D1 gene in HCC. Consequently, the intravenous injection of SF-PL/siGPC3 into nude mice bearing subcutaneous human HepG2 xenografts effectively inhibited tumor growth and also increased the survival rates of animals. These results revealed the great potential of the PEI-modified liposomal nanomedicine carrying SF and siGPC3 to improve HCC treatment.
Co-reporter:Chuyi Chen;Xinghua Huang;Yong Wang;Liteng Lin;Lei Liu;Guanyi Li;Shangchao Wu;Chaozhang Xu;Jianhua Zhou;Xintao Shuai
RSC Advances (2011-Present) 2017 vol. 7(Issue 18) pp:11057-11066
Publication Date(Web):2017/02/07
DOI:10.1039/C6RA28309H
Prostate cancer is one of the most common male malignancies, and MiR-21 plays an important role in the pathogenesis of this cancer. The treatment of microRNAs has proven to be a viable strategy for tumor therapy. However, the delivery of genes remains a major challenge because of the lack of efficient carriers. In this study, a diblock copolymer PEG–PAsp(DETA) of biocompatible polyethylene glycol (PEG) and biodegradable poly(L-aspartic acid) grafted with diethylenetriamine (PAsp(DETA)) was introduced as a delivery vector for an miR-21 inhibitor (i.e. antisense oligonucleotides for miR-21). Using in vitro and in vivo animal experiments, we studied the transfection efficiency and mechanism of action of the PEG–PAsp(DETA)/miR-21 inhibitor towards prostate cancer PC-3 cells. The biodegradable polymer mPEG–PAsp(DETA) was successfully used as a gene carrier to effectively transport the miR-21 inhibitor into PC-3 cells, which resulted in miR-21 silencing, upregulation of PDCD4 gene expression, and induced apoptosis in PC-3 prostate cancer. Meanwhile, the cytotoxicity of biodegradable carriers is very low. This study demonstrates the potential of our novel nucleic acid nanomedicine for the effective treatment of prostate cancer.
Co-reporter:Lu Zhang, Hong Xiao, Jingguo Li, Du Cheng and Xintao Shuai
Nanoscale 2016 vol. 8(Issue 25) pp:12608-12617
Publication Date(Web):14 Dec 2015
DOI:10.1039/C5NR07868G
Drug resistance is the underlying cause for therapeutic failure in clinical cancer chemotherapy. A prodrug copolymer mPEG-PAsp(DIP-co-BZA-co-DOX) (PDBD) was synthesized and assembled into a nanoscale vesicle comprising a PEG corona, a reduction and pH dual-sensitive hydrophobic membrane and an aqueous lumen encapsulating doxorubicin hydrochloride (DOX·HCl) and arsenite (As). The dual stimulation-sensitive design of the vesicle gave rise to rapid release of the physically entrapped DOX·HCl and arsenite inside acidic lysosomes, and chemically conjugated DOX inside the cytosol with high glutathione (GSH) concentration. In the optimized concentration range, arsenite previously recognized as a promising anticancer agent from traditional Chinese medicine can down-regulate the expressions of anti-apoptotic and multidrug resistance proteins to sensitize cancer cells to chemotherapy. Consequently, the DOX-As-co-loaded vesicle demonstrated potent anticancer activity. Compared to the only DOX-loaded vesicle, the DOX-As-co-loaded one induced more than twice the apoptotic ratio of MCF-7/ADR breast cancer cells at a low As concentration (0.5 μM), due to the synergistic effects of DOX and As. The drug loading strategy integrating chemical conjugation and physical encapsulation in stimulation-sensitive carriers enabled efficient drug loading in the formulation.
Co-reporter:Yong Wang, Hong Xiao, Jing Fang, Xingsu Yu, Zhenwei Su, Du Cheng and Xintao Shuai
Chemical Communications 2016 vol. 52(Issue 6) pp:1194-1197
Publication Date(Web):16 Nov 2015
DOI:10.1039/C5CC09181K
A novel siRNA delivery system based on a triblock copolymer with pH and reduction dual-sensitivity was introduced. The polyplex, having high delivery efficiency not dependent on surface charge reversion in response to the pH value of tumor tissue, was used for target gene silencing in cancer therapy.
Co-reporter:Guoyong Zhou, Yongmin Xu, Meiwan Chen, Du Cheng and Xintao Shuai
Polymer Chemistry 2016 vol. 7(Issue 23) pp:3857-3863
Publication Date(Web):09 May 2016
DOI:10.1039/C6PY00427J
A pH-sensitive ternary block copolymer comprising poly(ethylene glycol)methyl ether methacrylate (PEGMA), and pH-sensitive segments poly(2-(dimethylamino) ethylmethacrylate) (PDMA) and poly(2-(diisopropyl amino)ethyl methacrylate) (PDPA) (mal-PEGMA-b-PDPA-b-PDMA, PMDM) was synthesized. The copolymer effectively complexed with siRNA at pH 5.0 to form a polyplex which showed decreased positive charge along with the increase of pH value due to deprotonation of the PDPA block. The nearly non-charged polyplex at pH 7.4 exhibited enhanced stability and inertness in serum-containing media, which is favorable for a prolonged circulation time and reduced cytotoxicity. The pH-sensitivity of PDMA and PDPA also enhanced the lysosomal escape of polyplexes after endocytosis. Moreover, modification of the tumor-penetrating peptide iRGD endowed the polyplexes with effective intratumoral delivery and high transfection efficiency. A study using the luciferase expression assay achieved highly effective target gene silencing both in vitro and in vivo, which revealed the potential of our iRGD-modified and pH-sensitive siRNA polyplex as a promising siRNA delivery system in cancer treatment.
Co-reporter:Hao Li, Ping Wang, Xuan Wang, Tinghui Yin, Guofu Zhou, Xintao Shuai and Rongqin Zheng
Biomaterials Science 2016 vol. 4(Issue 6) pp:979-988
Publication Date(Web):28 Apr 2016
DOI:10.1039/C6BM00080K
A novel perfluorooctyl bromide (PFOB)-loaded nanovesicle with a size of about 500 nm was prepared by self-assembly of an amphiphilic block copolymer, poly(ethylene oxide)-b-poly(D,L-lactic acid) (PEG-PDLLA), for blood pool ultrasound imaging. The excellent compatibility of PFOB with the hydrophobic PDLLA block makes PFOB uniformly distribute and integrate well within the nanovesicle shell. In theory, both the compressibility and shell density of the nanovesicle as ultrasound scatterers are enhanced, resulting in much higher echo intensity compared to the other PFOB nanoparticles. In vitro and in vivo imaging results illustrate that these polymeric nanovesicles with extremely low content of PFOB show quite a good contrast-enhancing effect even if highly diluted in blood. Therefore this PFOB-loaded polymeric nanovesicle is anticipated to be applicable as an ultrasound contrast agent for normal angiography and specific imaging of capillary-abundant organs or tissues (e.g. tumors).
Co-reporter:Jingguo Li, Lu Zhang, Yujie Lin, Hong Xiao, Mingxiang Zuo, Du Cheng and Xintao Shuai
RSC Advances 2016 vol. 6(Issue 11) pp:9160-9163
Publication Date(Web):14 Jan 2016
DOI:10.1039/C5RA27293A
A novel tetra-doxorubicin-tailed polyethylene glycol via benzoic-imine bond linkage was synthesized and self-assembled to a pH-sensitive prodrug micelle. This micelle not only effectively entered cancer cells but also quickly released doxorubicin (DOX) in tumor sites to exert anticancer activity in vitro.
Co-reporter:Ping Wang, Tinghui Yin, Jingguo Li, Bowen Zheng, Xiaoli Wang, Yiru Wang, Jian Zheng, Rongqin Zheng, Xintao Shuai
Nanomedicine: Nanotechnology, Biology and Medicine 2016 Volume 12(Issue 4) pp:1139-1149
Publication Date(Web):May 2016
DOI:10.1016/j.nano.2015.12.361
RNA interfering is a gene therapeutic approach of great potential for cancer. However, tumor-targeted delivery of small interfering RNA (siRNA) solely based on the enhanced permeability and retention effect of nanocarriers is often insufficient. To address this challenge, siRNA encapsulated ultrasound-responsive microbubble (MB) was developed from polymeric siRNA micelles and liposomal MBs using hetero-assembling strategy. 1 MHz low-frequency ultrasound exposure of the tumor site after intratumoral injection of XIAP siRNA/MBs led to enhanced permeability for much more siRNA delivery into deep tumor regions. Significant improvement of XIAP gene silencing and cleaved caspase-3 activation was achieved, resulting in good therapeutic effect on human cervical cancer xenograft model in nude mice. Moreover, real-time US monitoring of the tumor was also possible using the siRNA/MBs as a contrast agent during the therapeutic process. These results show that the multi-functional siRNA/MBs are a promising theranostic system for cancer gene therapy.An siRNA-encapsulated US-responsive agent, which was developed from polymeric siRNA micelles and liposomal MBs using hetero-assembling strategy, was exposed by low-frequency US at the tumor site after intratumoral injection, leading to enhanced permeability of tumor tissues for much more effective delivery of siRNA into deep tumor regions and good therapeutic effect.
Co-reporter:Lu Wang, Yuanyuan Yuan, Shudong Lin, Jinsheng Huang, Jian Dai, Qing Jiang, Du Cheng, Xintao Shuai
Biomaterials 2016 78() pp: 40-49
Publication Date(Web):February 2016
DOI:10.1016/j.biomaterials.2015.11.024
Combined photothermo-chemotherapy is a new cancer treatment modality that improves therapeutic outcome by synergistic actions of two different means. A reduction and pH dual sensitive polymeric vesicle encapsulating doxorubicin (DOX) was prepared and then decorated with a gold layer using a modified method of in situ gold seed growth. By tuning the compactness of gold layer, the gold nanoshell may possess a desirable light absorption peak for tumor photothermal therapy using near-infrared (NIR) laser irradiation, a method featuring high tissue penetrability essential for in vivo applications. The NIR light energy was converted into heat, which killed cancer cells in the vicinity and induced the rupture of nanoshell to release DOX inside tumor. Therefore, a combined photothermo-chemotherapy of tumor can be achieved precisely at tumor site. In addition, DOX released in the thermochemotherapeutic mode effectively penetrated tumor tissue, which is meaningful considering the intrinsic low tissue penetrability of nanomedicines. In nude mice bearing human Bel-7402 hepatoma, the photothermo-chemotherapy using DOX-loaded gold nanoshell appeared advantageous over a chemotherapy or a photothermal therapy alone.
Co-reporter:Zhe Yang, Di Gao, Zhong Cao, Chao Zhang, Du Cheng, Jie Liu and Xintao Shuai
Biomaterials Science 2015 vol. 3(Issue 7) pp:1035-1049
Publication Date(Web):06 Feb 2015
DOI:10.1039/C4BM00369A
Cancer remains a major killer and a leading cause of death in the world; thus, a growing number of new treatments have been focused on cancer therapy over the past few decades. Chemotherapy, which is thought to be a powerful strategy for cancer treatment, has been widely used in clinical therapy in recent years. However, due to the complexity of cancer, a single therapeutic approach is insufficient for the suppression of cancer growth and migration. Therefore, increasing attention has been paid to the use of smart multifunctional carriers and combinatorially delivers chemotherapeutic drugs and functional genes in order to maximize therapeutic efficiency. Combination therapy using selected drugs and genes can not only overcome multidrug resistance and inhibit the cellular anti-apoptotic process but also achieve a synergistic therapeutic effect. Because multifunctional nanocarriers are important for achieving these goals, this review will illustrate and discuss some advanced biomaterial nanocarriers for co-delivering therapeutic genes and drugs, including multifunctional micelles, liposomes, polymeric conjugates and inorganic nanoparticles. In addition, the challenges and future perspectives for co-delivery systems, containing therapeutic drugs and genes to achieve better therapeutic effects for cancer treatment will be discussed.
Co-reporter:Jin Wang, Linglan Ren, Jingguo Li, Jinsheng Huang, Du Cheng and Xintao Shuai
RSC Advances 2015 vol. 5(Issue 27) pp:21103-21111
Publication Date(Web):17 Feb 2015
DOI:10.1039/C4RA16870D
Although RNA interference (RNAi) has demonstrated great potential in tumor therapy in recent years, the lack of an effective approach for non-invasive monitoring of in vivo siRNA delivery is still impeding its clinical application. Based on the biodegradable and redox-sensitive cationic polymer synthesized in our lab, an MRI-visible nanocarrier was prepared to codeliver siRNA and SPIO into HepG2 cancer cells. The highly efficient codelivery of siRNA and SPIO were achieved both in vitro and in vivo. Consequently, the survivin-specific siRNA delivered with the vector could effectively suppress the survivin gene expression and promote hepatic tumor cell apoptosis. Moreover, incorporation of SPIO made the siRNA delivery and therapy trackable with noninvasive magnetic resonance imaging (MRI), which in turn may provide real-time and reliable information to guide the optimization of carrier properties for targeted siRNA delivery.
Co-reporter:Jingguo Li;Xingsu Yu;Yong Wang;Yuanyuan Yuan;Hong Xiao;Du Cheng;Xintao Shuai
Advanced Materials 2014 Volume 26( Issue 48) pp:8217-8224
Publication Date(Web):
DOI:10.1002/adma.201403877
Co-reporter:Jingguo Li, Du Cheng, Tinghui Yin, Weicai Chen, Yujie Lin, Jifeng Chen, Ruitang Li and Xintao Shuai
Nanoscale 2014 vol. 6(Issue 3) pp:1732-1740
Publication Date(Web):26 Nov 2013
DOI:10.1039/C3NR05024F
siRNA therapy research has primarily focused on the synthesis and development of effective siRNA delivery vectors with easy biodegradability and low toxicity. In the present study, we synthesized a ternary copolymer mPEG-b-PLL-g-(ss-lPEI), denoted as PLI, by introducing disulfide bond linkages to graft low molecular weight linear polyethylenimine (lPEI) to the block copolymer of poly(L-lysine) (PLL) and poly(ethylene glycol) (PEG) for siRNA delivery. The PLL block and disulfide linkage rendered the carrier biodegradability, while lPEI grafting brought about the proton buffering capacity for lysosomal siRNA release and low cationic toxicity. Conjugation of a single chain monoclonal antibody (Herceptin) to the carrier as a targeting ligand for the Her2/neu receptor significantly increased the transfection activity of the copolymer/siRNA nanocomplex (i.e. the polyplex) in Skov-3, a human ovarian cancer cell line. Determination of gene expression at both the mRNA and protein levels demonstrated that Her2-targeted delivery of siRNA (XIAP siRNA) effectively downregulated the targeted XIAP (X-linked inhibitor of apoptosis protein) gene, resulting in enhanced cancer cell apoptosis and improved therapeutic efficacy in vitro and in vivo. The distinct features of low cytotoxicity, easy degradability, and high siRNA transfection efficiency make the copolymer a promising candidate for siRNA therapy in tumors.
Co-reporter:Lu Wang, Yuanyuan Yuan, Shudong Lin, Du Cheng, Xiaoying Wang, Qing Jiang and Xintao Shuai
Polymer Chemistry 2014 vol. 5(Issue 23) pp:6866-6866
Publication Date(Web):09 Oct 2014
DOI:10.1039/C4PY90073A
Correction for ‘Co-delivery of 5-fluorocytosine and cytosine deaminase into glioma cells mediated by an intracellular environment-responsive nanovesicle’ by Lu Wang et al., Polym. Chem., 2014, 5, 4542–4552.
Co-reporter:Lu Wang, Yuanyuan Yuan, Shudong Lin, Du Cheng, Xiaoying Wang, Qing Jiang and Xintao Shuai
Polymer Chemistry 2014 vol. 5(Issue 15) pp:4542-4552
Publication Date(Web):25 Mar 2014
DOI:10.1039/C4PY00291A
The diblock copolymer (PEI-PAsp(DIP/MEA)) of branched polyethyleneimine (PEI) and biodegradable poly(2-diisopropylamino/2-mercaptoethylamine) ethyl aspartate (PAsp(DIP/MEA)) was synthesized and assembled into nanovesicles for the co-delivery of cytosine deaminase (CD) gene and 5-fluorocytosine (pCMVCD/5-FC) into glioma cells. The nanovesicle comprises a hydrophilic outerlayer of branched PEI for pCMVCD complexation, a hydrophilic inner cavity for prodrug 5-FC loading, and a pH-sensitive membrane crosslinked by disulfide to prevent drug leakage into the bloodstream-simulating environment with neutral pH and without reducing agent. Yet, once the PPDM (PEI-PAsp(DIP/MEA)) nanovesicle was internalized into cancer cells and entrapped inside lysosomes featuring a low pH (∼5) and enriched reducing agent (∼10 mM GSH), it dissociated as a result of tertiary amine protonation and disulfide bond breakage to release the loaded drug. The in vitro release studies showed that less than 10% of 5-FC was released from the nanovesicle in 24 h at pH 7.4, whereas about 98% of 5-FC was released in the presence of 10 mM GSH at pH 5.0. The prodrug 5-FC was converted into its toxic active metabolite 5-fluorouracil (5-FU) by cytosine deaminase inside C6 glioma cells, owing to the effective CD gene transfection and expression. As a result, the 5-FC/pCMVCD-loaded nanovesicle induced effective apoptosis and generated a significant cytotoxic effect in the cancer cells. Our results indicated that this multifunctional nanovesicle is a promising carrier for the co-delivery of gene and drug or prodrug in cancer therapy.
Co-reporter:Tinghui Yin, Ping Wang, Jingguo Li, Yiru Wang, Bowen Zheng, Rongqin Zheng, Du Cheng, Xintao Shuai
Biomaterials 2014 35(22) pp: 5932-5943
Publication Date(Web):
DOI:10.1016/j.biomaterials.2014.03.072
Co-reporter:Linjuan Zeng, Jingguo Li, Yong Wang, Chenchen Qian, Yinting Chen, Qiubo Zhang, Wei Wu, Zhong Lin, Jianzhong Liang, Xintao Shuai, Kaihong Huang
Nanomedicine: Nanotechnology, Biology and Medicine 2014 Volume 10(Issue 2) pp:463-472
Publication Date(Web):February 2014
DOI:10.1016/j.nano.2013.08.007
The synergetic inhibitory effects on human pancreatic cancer by nanoparticle-mediated siRNA and arsenic therapy were investigated both in vitro and in vivo. Poly(ethylene glycol)-block-poly(l-lysine) were prepared to form siRNA-complexed polyplex and poly(ethylene glycol)-block-poly(dl-lactide) were prepared to form arsenic-encapsulated vesicle, respectively. Down-regulation of the mutant Kras gene by siRNA caused defective abilities of proliferation, clonal formation, migration, and invasion of pancreatic cancer cells, as well as cell cycle arrest at the G0/G1 phase, which substantially enhanced the apoptosis-inducing effect of arsenic administration. Consequently, co-administration of the two nanomedicines encapsulating siRNA or arsenic showed ideal tumor growth inhibition both in vitro and in vivo as a result of synergistic effect of the siRNA-directed Kras oncogene silencing and arsenic-induced cell apoptosis. These results suggest that the combination of mutant Kras gene silencing and arsenic therapy using nanoparticle-mediated delivery strategy is promising for pancreatic cancer treatment.From the Clinical EditorTreatment of pancreatic cancer remains a major challenge. These authors demonstrate a method that combines a siRNA-based Kras silencing with arsenic delivery to pancreatic cancer cells using nanoparticles, resulting in enhanced apoptosis induction in the treated cells.The siRNA was delivered by the efficient nonviral vector to knockdown mutant Kras gene in human pancreatic cancer cell line PANC-1, which led to the defective bio-functions of cancer cells in various aspects. Cytotoxic medicine arsenic (As) was also encapsulated in nanoparticles, the co-administration of the two nanomedicines encapsulating siRNA or As resulted in the enhanced tumor growth inhibition on PANC-1 cells both in vitro and in vivo.
Co-reporter:Yiru Wang, Jing Fang, Du Cheng, Yong Wang, Xintao Shuai
Polymer 2014 Volume 55(Issue 15) pp:3217-3226
Publication Date(Web):25 June 2014
DOI:10.1016/j.polymer.2014.05.038
Aiming to effectively codeliver chemotherapeutic drugs (DOX) and siRNA (BCL-2 siRNA) into tumor cells, well-defined triblock copolymers composed of hydrophilic and hydrophobic blocks were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. The poly(ethylene glycol) (PEG) macroRAFT agent and two pH-sensitive monomers (2-(diethylamino)ethyl methacrylate, DEA and 2-(dimethylamino)ethyl methacrylate, DMA) were used for synthesizing the copolymers consisting of pH-sensitive PDEA, PDMA and PEG blocks. At pH 10, the copolymer in aqueous solution self-assembled into a micelle with hydrophobic core consisting of PDEA and PDMA for doxorubicin (DOX) encapsulation, owing to the deprotonation of the side tertiary amino groups. At neutral pH, the hydrophobic core became porous and positively charged to allow siRNA complexation due to PDMA solubilization (the pKa of PDMA is around 8.0). Inside the acidic lysosomal compartments, PDEA was protonated and thus became hydrophilic to result in rapid release of DOX. Moreover, existence of two pH-sensitive blocks PDMA and PDEA endowed the copolymer with proton buffering effect that facilitated lysosomal escape of nanocomplex and siRNA release inside cells. Our results showed that the two codelivered therapeutic agents acted synergistically on the human hepatic carcinoma HepG2 cells to induce apoptosis in a highly effective manner.
Co-reporter:Yinting Chen;Guoda Lian;Chengde Liao;Weiwei Wang
Journal of Gastroenterology 2013 Volume 48( Issue 7) pp:809-821
Publication Date(Web):2013 July
DOI:10.1007/s00535-012-0713-x
Gene therapy is a promising therapeutic method but is severely hampered due to its lack of an ideal delivery system. Therefore, in this study, a nonviral and magnetic resonance imaging (MRI) visible vector, polyethylene glycol-grafted polyethylenimine and superparamagnetic iron oxide nanoparticles (PEG-g-PEI-SPION) was used as a nanocarrier for small interfering RNA (siRNA) delivery in gastric cancer.Biophysical characterization of PEG-g-PEI-SPION was systematically analyzed, including size, zeta potential, siRNA condensation capacity, cell viability, transfection efficiency, cellular uptake, and MRI-visible function in vivo. Besides, CD44 variant isoform 6 (CD44v6), a protein marker for metastatic behavior in gastric cancer, and was chose as the target gene to further analyze the siRNA delivery function of PEG-g-PEI-SPION.Under comprehensive analysis, the appropriate N/P ratio of PEG-g-PEI-SPION/siRNA was 10,. and siRNA targeting at human CD44v6 (siCD44v6) transferred by PEG-g-PEI-SPION was effective at downregulating the CD44v6 expression of gastric carcinoma cell line SGC-7901 in vitro. Moreover, knockdown of CD44v6 impaired migrating and invasive abilities of SGC-7901 cells. Furthermore, PEG-g-PEI-SPION was a highly efficient contrast agent for MRI scan in vivo.PEG-g-PEI-SPION was a promising nonviral vector with molecular image tracing capacity for cancer gene therapy. And CD44v6 was a potential target gene for the prevention and detection of metastatic behavior in gastric cancer.
Co-reporter:Tinghui Yin, Ping Wang, Jingguo Li, Rongqin Zheng, Bowen Zheng, Du Cheng, Ruitang Li, Jieyi Lai, Xintao Shuai
Biomaterials 2013 34(18) pp: 4532-4543
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.02.067
Co-reporter:Chenchen Qian, Yong Wang, Yinting Chen, Linjuan Zeng, Qiubo Zhang, Xintao Shuai, Kaihong Huang
Biomaterials 2013 34(26) pp: 6175-6184
Publication Date(Web):
DOI:10.1016/j.biomaterials.2013.04.056
Co-reporter:Weiwei Wang;Du Cheng;Faming Gong;Xiangmin Miao;Xintao Shuai
Advanced Materials 2012 Volume 24( Issue 1) pp:115-120
Publication Date(Web):
DOI:10.1002/adma.201104066
Co-reporter:Xiangmin Miao, Liansheng Ling, Du Cheng and Xintao Shuai
Analyst 2012 vol. 137(Issue 13) pp:3064-3069
Publication Date(Web):13 Apr 2012
DOI:10.1039/C2AN35217F
Copper ion (Cu2+) plays an important role in many biological reactions, and a suitable level of Cu2+ is necessary for the regular metabolism of life. Thus developing a sensitive and simple method for determination of Cu2+ is essential. Here, a novel and sensitive Cu2+ sensor was developed based on detecting the average hydrodynamic diameter of AuNPs by using dynamic light scattering (DLS). Cu2+-specific DNAzyme was double-strand and could not adsorb on the surface of AuNPs, accordingly AuNPs aggregation would occur with the addition of NaCl. However, Cu2+ could cleave DNAzyme and release single-stranded DNA (ssDNA) fragments, which could adsorb on the surface of AuNPs and prevent them from aggregation. Such differences in DNA adsorption ability on AuNPs before and after the addition of Cu2+ affected the disperse state of AuNPs directly, and then affected their average hydrodynamic diameter, which could be detected with the DLS technique. Based upon the above mentioned principle, detection of Cu2+ could be realized over the range from 100 pM to 2.0 nM, with a linear regression equation of D = 306.73 − 89.66C (C: nM, R = 0.9953) and a detection limit of 60 pM (3δ/slope). Moreover, satisfactory results were obtained when the assay was applied in the detection of Cu2+ in water samples.
Co-reporter:Xiang-Min Miao, Lian-Sheng Ling, Xin-Tao Shuai
Analytical Biochemistry 2012 Volume 421(Issue 2) pp:582-586
Publication Date(Web):15 February 2012
DOI:10.1016/j.ab.2011.11.031
Lead ion (Pb2+) accumulation in nature can affect the environment and human health severely. Thus, rapid and sensitive detection is of great importance. One-step detection of Pb2+ at attomole levels was realized by using dynamic light scattering (DLS) technique coupled with unmodified gold nanoparticles (AuNPs). Pb2+-dependent DNAzyme was double-stranded and could not adsorb on the surface of AuNPs, while the substrate strand could be cleaved into ssDNA fragments on addition of Pb2+. The ssDNA fragments could adsorb on the surface of AuNPs and prevent them from aggregating in the presence of NaCl. Therefore, the disperse state of AuNPs changed on addition of Pb2+ in the presence of DNAzyme and NaCl, which was estimated with an average hydrodynamic diameter by using DLS. Under optimum conditions, the average diameter of the solution decreased linearly with the concentration of Pb2+ over the range from 10 to 300 pM, with a detection limit of 6.2 pM. Moreover, satisfactory results were obtained when the proposed method was applied in the detection of Pb2+ in water samples.
Co-reporter:Cuiping Guo, Weicai Chen, Shudong Lin, Hao Li, Du Cheng, Xiaoying Wang, Xintao Shuai
Polymer 2012 Volume 53(Issue 2) pp:342-349
Publication Date(Web):24 January 2012
DOI:10.1016/j.polymer.2011.12.008
A series of Poly(l-lysine)m-b-poly[N-(N′,N′-diisopropylaminoethyl) aspartamide]n copolymers, abbreviated as PLLm-b-P[Asp(DIP)]n were designed and synthesized via ring-opening polymerization(ROP), click chemistry, aminolysis and hydrolysis. Using 1H NMR, FT-IR and GPC, the structures and compositions of these copolymers have been verified. Through feed ratio control, block copolymer PLLm-b-P[Asp(DIP)]n with different PLL and PAsp(DIP) block lengths were obtained, which can be modified to adjust the pH responsiveness and the self-assembling behaviors of the PLLm-b-P[Asp(DIP)]n. From the results of DLS, TEM and 1H NMR, these block copolymers can form stable micelles with a partially hydrated PAsp(DIP) core and a PLL corona at pH 7.4. While as demonstrated by 1H NMR and TEM, these PLLm-b-P[Asp(DIP)]n micelle was disassembled due to further protonation of the tertiary amine in the PAsp(DIP) block at pH 5.4. These pH responsive character of the PLLm-b-P[Asp(DIP)]n micelles made them as potential pH responsive gene delivery system which may co-deliver drug and DNA simultaneously.
Co-reporter:Du Cheng, Nuo Cao, Jifeng Chen, Xingsu Yu, Xintao Shuai
Biomaterials 2012 33(4) pp: 1170-1179
Publication Date(Web):
DOI:10.1016/j.biomaterials.2011.10.057
Co-reporter:Yu Guo, Wenjie Chen, Weiwei Wang, Jun Shen, Ruomi Guo, Faming Gong, Shudong Lin, Du Cheng, Guihua Chen, and Xintao Shuai
ACS Nano 2012 Volume 6(Issue 12) pp:10646
Publication Date(Web):November 28, 2012
DOI:10.1021/nn3037573
As the final life-saving treatment option for patients with terminal organ failure, organ transplantation is far from an ideal solution. The concomitant allograft rejection, which is hardly detectable especially in the early acute rejection (AR) period characterized by an intense cellular and humoral attack on donor tissue, greatly affects the graft survival and results in rapid graft loss. Based on a magnetic resonance imaging (MRI)-visible and T-cell-targeted multifunctional polymeric nanocarrier developed in our lab, effective co-delivery of pDNA and superparamagnetic iron oxide nanoparticles into primary T cells expressing CD3 molecular biomarker was confirmed in vitro. In the heart transplanted rat model, this multifunctional nanocarrier showed not only a high efficiency in detecting post-transplantation acute rejection but also a great ability to mediate gene transfection in T cells. Upon intravenous injection of this MRI-visible polyplex of nanocarrier and pDNA, T-cell gathering was detected at the endocardium of the transplanted heart as linear strongly hypointense areas on the MRI T2*-weighted images on the third day after cardiac transplantation. Systematic histological and molecular biology studies demonstrated that the immune response in heart transplanted rats was significantly suppressed upon gene therapy using the polyplex bearing the DGKα gene. More excitingly, the therapeutic efficacy was readily monitored by noninvasive MRI during the treatment process. Our results revealed the great potential of the multifunctional nanocarrier as a highly effective imaging tool for real-time and noninvasive monitoring and a powerful nanomedicine platform for gene therapy of AR with high efficiency.Keywords: heart allograft rejection; magnetic resonance imaging; nanoparticle; single-chain antibody; T-cell targeting
Co-reporter:Qiquan Sun, Du Cheng, Xingsu Yu, Zuoquan Zhang, Jian Dai, Hao Li, Biling Liang and Xintao Shuai
Journal of Materials Chemistry A 2011 vol. 21(Issue 39) pp:15316-15326
Publication Date(Web):25 Aug 2011
DOI:10.1039/C1JM12404H
Diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable 2-(diisopropylamino)ethanol grafted poly(L-aspartic acid) (PAsp(DIP)) were synthesized and evaluated as a MRI-visible and pH-sensitive drug delivery system. The copolymers can self-assemble into stable vesicles in aqueous solutions at neutral pH, resembling the physiological environment, whereas they disassemble in acidic endosomal/lysosomal compartments of tumor cells to achieve rapid drug release. The anticancer drug doxorubicin (DOX) and hydrophilic superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated inside the inner aqueous core of the vesicles for cancer therapy and MR imaging, respectively. In vitrodrug release studies showed that the DOX release from the pH-sensitive vesicles was significantly faster at pH 5.0 than at pH 7.4. SPIONs clustering inside the inner aqueous core of the vesicles resulted in a high spin–spin (T2) relaxivity. Cell culture studies showed that the DOX-SPION-loaded vesicles could be effectively internalized by human hepatic cancer Bel 7402 cells, and DOX could be rapidly released from vesicles inside lysosomal compartments and then migrated into nuclei. Consequently effective suppression of cancer cell growth was detected. This study demonstrated the potential of the biodegradable DOX-SPION-loaded pH-sensitive vesicles as an effective multifunctional nanomedicine platform for cancer therapy due to their pH-triggerable drug release and high MRI sensitivity.
Co-reporter:Du Cheng, Guobin Hong, Weiwei Wang, Renxu Yuan, Hua Ai, Jun Shen, Biling Liang, Jinming Gao and Xintao Shuai
Journal of Materials Chemistry A 2011 vol. 21(Issue 13) pp:4796-4804
Publication Date(Web):04 Feb 2011
DOI:10.1039/C0JM03783D
Copolymers of poly(ethylene glycol) and poly(ε-caprolactone) bearing folate as a targeting molecule, i.e. Fa–PEG–PCL, are synthesized and employed to encapsulate nonclustered superparamagnetic iron oxide nanoparticle (SPION) to achieve a water-dispersible and tumor-targeted MRI contrast agent. Compared to the water-soluble SPIONs prepared by small molecular surfactant coating, the nonclustered SPIO-encapsulated PEG–PCL micelles (PEG–PCL–SPIONs) simultaneously display increased transversal (r2) and much decreased longitudinal (r1) magnetic resonance relaxivities, leading to high r2/r1 ratios which make PEG–PCL–SPIONs highly sensitive MRI T2 contrast agents. Animal experiments are carried out by injecting the micelle solutions via a tail vein into nude mice bearing subcutaneous xenografts of human Bel 7402 hepatoma. Notably, the nonclustered SPIO-encapsulated micelles measuring 35 nm on average based on PEG4.3k–PCL1k display much slower liver accumulation implying prolonged circulation, compared to the clustered SPIO-encapsulated micelles (125 nm) based on PEG4.3k–PCL7.2k. Furthermore, injection of the small-sized and folate-targeted micelle, i.e. Fa–PEG4.3k–PCL1k–SPION, result in obviously shortened MRI T2 as well as much decreased MRI signal intensity within the tumor section, implying efficient accumulation of the micelles which is also demonstrated by prussian blue staining of the tumor tissue. Our results reveal the great potential of the nonclustered SPIO-encapsulated and small-sized micelle with active tumor-targeting function as an effective MRI probe for in vivo tumor detection.
Co-reporter:Xiangmin Miao, Liansheng Ling and Xintao Shuai
Chemical Communications 2011 vol. 47(Issue 14) pp:4192-4194
Publication Date(Web):02 Mar 2011
DOI:10.1039/C0CC05344A
A dynamic light scattering sensor for Pb2+ was constructed with oligonucleotide-modified gold nanoparticles based upon its cleavage property for DNAzyme.
Co-reporter:Dr. Jian Dai;Shudong Lin;Dr. Du Cheng;Seyin Zou; Xintao Shuai
Angewandte Chemie 2011 Volume 123( Issue 40) pp:9576-9580
Publication Date(Web):
DOI:10.1002/ange.201103806
Co-reporter:Jian Dai, Seyin Zou, Yuanyuan Pei, Du Cheng, Hua Ai, Xintao Shuai
Biomaterials 2011 32(6) pp: 1694-1705
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.10.044
Co-reporter:Nuo Cao, Du Cheng, Seyin Zou, Hua Ai, Jinming Gao, Xintao Shuai
Biomaterials 2011 32(8) pp: 2222-2232
Publication Date(Web):
DOI:10.1016/j.biomaterials.2010.11.061
Co-reporter:Dr. Jian Dai;Shudong Lin;Dr. Du Cheng;Seyin Zou; Xintao Shuai
Angewandte Chemie International Edition 2011 Volume 50( Issue 40) pp:9404-9408
Publication Date(Web):
DOI:10.1002/anie.201103806
Co-reporter:Xiang-Min Miao;Cen Xiong;Wei-Wei Wang;Dr. Lian-Sheng Ling;Dr. Xin-Tao Shuai
Chemistry - A European Journal 2011 Volume 17( Issue 40) pp:11230-11236
Publication Date(Web):
DOI:10.1002/chem.201003010
Abstract
An ultrasensitive and simple dynamic-light-scattering (DLS) assay for the sequence-specific recognition of double-stranded DNA (dsDNA) was developed based on detection of the average diameter change of Au nanoparticle (AuNP) probes modified with oligonucleotides 5′-TTTCTCTTCCTT- CTCTTC-(T)12-SH-3′ (Oligo 1) and 5′-TTCTTTCTTTTCTTTTTC-(T)12- SH-3′ (Oligo 2). The target dsDNA was composed of two complementary oligonucleotides: 5′-AAAGAGAAGGAAGAGAAGAAGAAAGAAAAGAAAAAG-3′ (Oligo 3) and 3′-TTTCTCTTCCTTCTCTTCTTCTTTCTTTTCTTTTTC-5′ (Oligo 4). Hybridization of the two AuNPs–Oligo probes with the target dsDNA induced aggregation of the target dsDNA by forming triplex DNA, which accordingly increased the average diameter. This diameter change could then be detected by DLS. The average diameter was proportional to the target dsDNA concentration over the range from 593 fM to 40 pM, with a detection limit of 593 fM. Moreover, the assay had good sequence specificity for the target dsDNA.
Co-reporter:Wenlong Zhang, Yanli Li, Lixin Liu, Qiquan Sun, Xintao Shuai, Wen Zhu and Yongming Chen
Biomacromolecules 2010 Volume 11(Issue 5) pp:
Publication Date(Web):April 20, 2010
DOI:10.1021/bm100116g
Amphiphilic poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate-g-poly(ε-caprolactone)) (PEG-b-P(HEMA-g-PCL)) toothbrushlike copolymers were synthesized and evaluated as drug delivery carriers. Two toothbrushlike polymers were synthesized via ring-opening polymerization of ε-caprolactone (CL) initiated by poly(ethylene glycol)-b-poly(2-hydroxyethyl methacrylate) (PEG-b-PHEMA) macromolecular initiators, and their molecular structures and physical properties were characterized using 1H NMR, gel permeation chromatography (GPC), and differential scanning calorimetric analysis (DSC). The melting points and crystallizable temperature have been decreased obviously, implying that the PCL cores of PEG-b-P(HEMA-g-PCL) toothbrushlike copolymer micelles with shorter PCL segments were unlikely to crystallize at room temperature for drug delivery application. Also the micellization properties of toothbrushlike copolymers in aqueous solution were investigated by fluorescence spectroscopy, dynamic light scattering (DLS), and transmission electron microscopy (TEM). Compared with the micelles from linear PEG-b-PCL block copolymers, the micelles of PEG-b-P(HEMA-g-PCL)s exhibited higher loading capacity to the anticancer drug, doxorubicin (DOX), and the drug-loaded micelles were highly stable in aqueous solution. In vitro DOX release data and confocal laser scanning microscopy (CLSM) studies showed that DOX-loaded toothbrushlike copolymer micelles could be effectively internalized by bladder carcinoma EJ cells, and the DOX could be released into endocytic compartments and finally transported to the nucleus. Such toothbrushlike copolymer micelles can be analogues of linear PEG-b-PCL diblock copolymers, but demonstrated better properties of loading and release due to their hydrophobic PCL cores do not crystallize at delivery conditions.
Co-reporter:JianHua Zhou;Lü Huang;WeiWei Wang;Jun Pang;Yang Zou
Science Bulletin 2009 Volume 54( Issue 18) pp:3137-3146
Publication Date(Web):2009 September
DOI:10.1007/s11434-009-0256-6
Methoxyl poly (ethylene glycol) (mPEG-OH) was successfully grafted onto branched polyethyleneimine (hy-PEI) to yield a water soluble graft copolymer mPEG-g-PEI. This copolymer may package super-paramagnetic iron oxide (SPIO) by ligand exchange. The SPIO weight percentage in the polymer coated nanoparticles was determined to be 55%, the size and zeta potential of nanoparticles was 50 nm and 12 mV respectively. Antibody fixation onto the complex (mPEI-g-PEG-SPIO) surface layer was achieved by activated single chain monoclonal antibody against prostate stem cell antigen (PSCA). Our study showed that the single chain antibody functionalized nanoprobe (scAbPSCA-PEI-g-PEG-SPIO) with a small size can specifically enter the prostate cancer cells, decreasing MRI T2-weighted signal intensity of prostate cancer cells to 44.76%. Our results revealed that the potential of this magnetic nanoparticulate system promised as a novel MRI nanoprobe for early diagnosis of prostate cancer (PCa).
Co-reporter:Xiaoqiang Yang;Bo Zhu;Tungalag Dong;Pengju Pan;Xintao Shuai;Yoshio Inoue
Macromolecular Bioscience 2008 Volume 8( Issue 12) pp:1116-1125
Publication Date(Web):
DOI:10.1002/mabi.200800085
Co-reporter:Xiaoqiang Yang;Wenjing Deng;Liwu Fu;Elvin Blanco;Jinming Gao;Daping Quan;Xintao Shuai
Journal of Biomedical Materials Research Part A 2008 Volume 86A( Issue 1) pp:48-60
Publication Date(Web):
DOI:10.1002/jbm.a.31537
Abstract
To overcome multidrug resistance (MDR) existing in tumor chemotherapy, polymeric micelles encoded with folic acid on the micelle surface were prepared with the encapsulation of a potent MDR modulator, FG020326. The micelles were fabricated from diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable poly(ε-caprolactone) (PCL) with folate attached to the distal ends of PEG chains. The folate-conjugated copolymers, folate-PEG-PCL, were synthesized by multistep chemical reactions. First, allyl-terminated copolymer (allyl-PEG-PCL) was synthesized through a ring-opening polymerization of ε-caprolactone in bulk employing monoallyl-PEG as a macroinitiator. Second, the allyl terminal groups of copolymers were converted into primary amino groups by a radical addition reaction, followed by conjugation of the carboxylic group of folic acid. In vitro studies at 37°C demonstrated that FG020326 release from micelles at pH 5.0 was faster than that at pH 7.4. Cytotoxicity studies with MTT assays indicated that folate-functionalized and FG020326-loaded micelles resensitized the cells approximately five times more than their folate-free counterparts (p < 0.01) in human KBv200 cells treated with vincristine (VCR). The in vitro Rhodamine 123 efflux experiment using MDR KBv200 cells revealed that when cells were pretreated with folate-attached and FG020326-loaded micelles, the P-glycoprotein (P-gp) drug efflux function was significantly inhibited. © 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2008
Co-reporter:Renxu Yuan ;Xintao Shuai
Journal of Polymer Science Part B: Polymer Physics 2008 Volume 46( Issue 8) pp:782-790
Publication Date(Web):
DOI:10.1002/polb.21412
Abstract
A poly(ethylene glycol)-b-poly(L-lysine) diblock copolymer (PEG-b-PLL) was synthesized. Micellization of this hydrophilic copolymer due to the block-specific threading of α-cyclodextrin (α-CD) molecules onto the polyethylene glycol (PEG) block yielded supramolecular-structured nanoparticles, which undergoes pH-inducible gelation in aqueous media. The pH-inducible gelation of supramolecular micelle in water appeared to be completely reversible upon pH changes. The synergetic effect of selective complexation between PEG block and α-CD and the pH-inducible hydrophobic interaction between PLL blocks at pH 10 was believed to be the driving force for the formation of the supramolecular hydrogel. 1H NMR and wide angle X-ray diffraction (WAXD) were employed to confirm the inclusion complexation between α-CD and PEG block. Meanwhile, the morphology of the micellized nanoparticles was investigated by transmission electron microscopy (TEM). The thermal stability of inclusion complexes (ICs) was investigated and the rheologic experiment was conducted to reveal the micelle-gel transition. Such pH-induced reversible micelle-gel transition of the supramolecular aggregates may find applications in several fields, for example as advanced biomedical material possessing stimulus-responsiveness. © 2008 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 46: 782–790, 2008
Co-reporter:Guobin Hong;Renxu Yuan;Biling Liang;Jun Shen;Xiaoqiang Yang
Biomedical Microdevices 2008 Volume 10( Issue 5) pp:693-700
Publication Date(Web):2008 October
DOI:10.1007/s10544-008-9180-9
Targeted delivery is a highly desirable strategy to improve the diagnostic imaging and therapeutic outcome because of enhanced efficacy and reduced toxicity. In the current research, anticancer drug doxorubicin (DOX) and contrast agent for magnetic resonance imaging (MRI), herein superparamagnetic ion oxide Fe3O4 (SPIO), were accommodated in the core of micelles self-assembled from amphiphilic block copolymer of poly(ethylene glycol) (PEG) and poly(ɛ-caprolactone) (PCL) with a targeting ligand (folate) attached to the distal ends of PEG (Folate-PEG-PCL). The in vitro tumor cell targeting efficacy of these folate functionalized and DOX/SPIO-loaded micelles (Folate-SPIO-DOX-Micelles) was evaluated upon observing cellular uptake of micelles by human hepatic carcinoma cells (Bel 7402 cells) which overexpresses surface receptors for folic acid. In the Prussian blue staining experiments, cells incubated with Folate-SPIO-DOX-Micelles showed much higher intracellular iron density than the cells incubated with the folate-free SPIO-DOX-Micelles. According to the flow cytometry data, cellular DOX uptake observed for the folate targeting micelle was about 2.5 fold higher than that for the non-targeting group. Furthermore, MTT assay showed that Folate-SPIO-DOX-Micelles effectively inhibited cell proliferation, while the folate-free SPIO-DOX-Micelles did not show the same feat at comparable DOX concentrations. The potential of Folate-SPIO-DOX-Micelle as a novel MRI-visible nanomedicine platform was assessed with a 1.5 T clinical MRI scanner. The acquired MRI T2 signal intensity of cells treated with the folate targeting micelles decreased significantly. By contrast, T2 signal did not show obvious decrease for cells treated with the folate-free micelles. Our results indicate that the multifunctional polymeric micelles, Folate-SPIO-DOX-Micelles, have better targeting tropism to the hepatic carcinoma cells in vitro than their non-targeting counterparts, and the cell targeting events of micelles can be monitored using a clinical MRI scanner.
Co-reporter:Xiangmin Miao, Liansheng Ling and Xintao Shuai
Chemical Communications 2011 - vol. 47(Issue 14) pp:NaN4194-4194
Publication Date(Web):2011/03/02
DOI:10.1039/C0CC05344A
A dynamic light scattering sensor for Pb2+ was constructed with oligonucleotide-modified gold nanoparticles based upon its cleavage property for DNAzyme.
Co-reporter:Hao Li, Ping Wang, Xuan Wang, Tinghui Yin, Guofu Zhou, Xintao Shuai and Rongqin Zheng
Biomaterials Science (2013-Present) 2016 - vol. 4(Issue 6) pp:NaN988-988
Publication Date(Web):2016/04/28
DOI:10.1039/C6BM00080K
A novel perfluorooctyl bromide (PFOB)-loaded nanovesicle with a size of about 500 nm was prepared by self-assembly of an amphiphilic block copolymer, poly(ethylene oxide)-b-poly(D,L-lactic acid) (PEG-PDLLA), for blood pool ultrasound imaging. The excellent compatibility of PFOB with the hydrophobic PDLLA block makes PFOB uniformly distribute and integrate well within the nanovesicle shell. In theory, both the compressibility and shell density of the nanovesicle as ultrasound scatterers are enhanced, resulting in much higher echo intensity compared to the other PFOB nanoparticles. In vitro and in vivo imaging results illustrate that these polymeric nanovesicles with extremely low content of PFOB show quite a good contrast-enhancing effect even if highly diluted in blood. Therefore this PFOB-loaded polymeric nanovesicle is anticipated to be applicable as an ultrasound contrast agent for normal angiography and specific imaging of capillary-abundant organs or tissues (e.g. tumors).
Co-reporter:Du Cheng, Guobin Hong, Weiwei Wang, Renxu Yuan, Hua Ai, Jun Shen, Biling Liang, Jinming Gao and Xintao Shuai
Journal of Materials Chemistry A 2011 - vol. 21(Issue 13) pp:NaN4804-4804
Publication Date(Web):2011/02/04
DOI:10.1039/C0JM03783D
Copolymers of poly(ethylene glycol) and poly(ε-caprolactone) bearing folate as a targeting molecule, i.e. Fa–PEG–PCL, are synthesized and employed to encapsulate nonclustered superparamagnetic iron oxide nanoparticle (SPION) to achieve a water-dispersible and tumor-targeted MRI contrast agent. Compared to the water-soluble SPIONs prepared by small molecular surfactant coating, the nonclustered SPIO-encapsulated PEG–PCL micelles (PEG–PCL–SPIONs) simultaneously display increased transversal (r2) and much decreased longitudinal (r1) magnetic resonance relaxivities, leading to high r2/r1 ratios which make PEG–PCL–SPIONs highly sensitive MRI T2 contrast agents. Animal experiments are carried out by injecting the micelle solutions via a tail vein into nude mice bearing subcutaneous xenografts of human Bel 7402 hepatoma. Notably, the nonclustered SPIO-encapsulated micelles measuring 35 nm on average based on PEG4.3k–PCL1k display much slower liver accumulation implying prolonged circulation, compared to the clustered SPIO-encapsulated micelles (125 nm) based on PEG4.3k–PCL7.2k. Furthermore, injection of the small-sized and folate-targeted micelle, i.e. Fa–PEG4.3k–PCL1k–SPION, result in obviously shortened MRI T2 as well as much decreased MRI signal intensity within the tumor section, implying efficient accumulation of the micelles which is also demonstrated by prussian blue staining of the tumor tissue. Our results reveal the great potential of the nonclustered SPIO-encapsulated and small-sized micelle with active tumor-targeting function as an effective MRI probe for in vivo tumor detection.
Co-reporter:Yong Wang, Hong Xiao, Jing Fang, Xingsu Yu, Zhenwei Su, Du Cheng and Xintao Shuai
Chemical Communications 2016 - vol. 52(Issue 6) pp:NaN1197-1197
Publication Date(Web):2015/11/16
DOI:10.1039/C5CC09181K
A novel siRNA delivery system based on a triblock copolymer with pH and reduction dual-sensitivity was introduced. The polyplex, having high delivery efficiency not dependent on surface charge reversion in response to the pH value of tumor tissue, was used for target gene silencing in cancer therapy.
Co-reporter:Zhe Yang, Di Gao, Zhong Cao, Chao Zhang, Du Cheng, Jie Liu and Xintao Shuai
Biomaterials Science (2013-Present) 2015 - vol. 3(Issue 7) pp:NaN1049-1049
Publication Date(Web):2015/02/06
DOI:10.1039/C4BM00369A
Cancer remains a major killer and a leading cause of death in the world; thus, a growing number of new treatments have been focused on cancer therapy over the past few decades. Chemotherapy, which is thought to be a powerful strategy for cancer treatment, has been widely used in clinical therapy in recent years. However, due to the complexity of cancer, a single therapeutic approach is insufficient for the suppression of cancer growth and migration. Therefore, increasing attention has been paid to the use of smart multifunctional carriers and combinatorially delivers chemotherapeutic drugs and functional genes in order to maximize therapeutic efficiency. Combination therapy using selected drugs and genes can not only overcome multidrug resistance and inhibit the cellular anti-apoptotic process but also achieve a synergistic therapeutic effect. Because multifunctional nanocarriers are important for achieving these goals, this review will illustrate and discuss some advanced biomaterial nanocarriers for co-delivering therapeutic genes and drugs, including multifunctional micelles, liposomes, polymeric conjugates and inorganic nanoparticles. In addition, the challenges and future perspectives for co-delivery systems, containing therapeutic drugs and genes to achieve better therapeutic effects for cancer treatment will be discussed.
Co-reporter:Qiquan Sun, Du Cheng, Xingsu Yu, Zuoquan Zhang, Jian Dai, Hao Li, Biling Liang and Xintao Shuai
Journal of Materials Chemistry A 2011 - vol. 21(Issue 39) pp:NaN15326-15326
Publication Date(Web):2011/08/25
DOI:10.1039/C1JM12404H
Diblock copolymers of poly(ethylene glycol) (PEG) and biodegradable 2-(diisopropylamino)ethanol grafted poly(L-aspartic acid) (PAsp(DIP)) were synthesized and evaluated as a MRI-visible and pH-sensitive drug delivery system. The copolymers can self-assemble into stable vesicles in aqueous solutions at neutral pH, resembling the physiological environment, whereas they disassemble in acidic endosomal/lysosomal compartments of tumor cells to achieve rapid drug release. The anticancer drug doxorubicin (DOX) and hydrophilic superparamagnetic iron oxide nanoparticles (SPIONs) were encapsulated inside the inner aqueous core of the vesicles for cancer therapy and MR imaging, respectively. In vitrodrug release studies showed that the DOX release from the pH-sensitive vesicles was significantly faster at pH 5.0 than at pH 7.4. SPIONs clustering inside the inner aqueous core of the vesicles resulted in a high spin–spin (T2) relaxivity. Cell culture studies showed that the DOX-SPION-loaded vesicles could be effectively internalized by human hepatic cancer Bel 7402 cells, and DOX could be rapidly released from vesicles inside lysosomal compartments and then migrated into nuclei. Consequently effective suppression of cancer cell growth was detected. This study demonstrated the potential of the biodegradable DOX-SPION-loaded pH-sensitive vesicles as an effective multifunctional nanomedicine platform for cancer therapy due to their pH-triggerable drug release and high MRI sensitivity.
