Xintao Shuai

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (103)552.77 Total impact

  • Jingguo Li · lu zhang · Yujie Lin · Hong Xiao · Mingxiang Zuo · Du Cheng · Xintao Shuai
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    ABSTRACT: 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 site to exert anticancer activity in vitro.
    No preview · Article · Jan 2016 · RSC Advances
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    ABSTRACT: Since the primary surgical treatment options for hepatocellular carcinoma (HCC), including hepatic resection and liver transplantation, often fail due to recurrence and metastasis, identifying early prognostic biomarkers and therapeutic targets for HCC is of great importance. This study shows that transducin beta-like protein 1-related protein (TBLR1) is a key HCC oncogene that plays important roles in HCC proliferation, antiapoptosis and angiogenesis by regulating the Wnt/β-catenin pathway. The folate-targeted theranostic siRNA nanomedicine Fa-PEG-g-PEI-SPION/psiRNA-TBLR1 effectively silences the TBLR1 gene in different human HCC cell lines in vitro and in human HCC samples in vivo, resulting in the simultaneous suppression of HCC cell proliferation, antiapoptosis and angiogenesis. Due to its multi-anticancer functions against HCC, intravenous injection of the folate-targeted siRNA nanomedicine into nude mice bearing intrahepatic or subcutaneous xenografts of human HCC has a significant therapeutic effect. Tumor growth in those animals was almost completely inhibited by treatment with Fa-PEG-g-PEI-SPION/psiRNA-TBLR1. Moreover, the SPION-encapsulated polyplexes possesses high MRI detection sensitivity, which makes tumor-targeted siRNA delivery easily trackable using the clinical MRI technique. In conclusion, the theranostic siRNA nanomedicine examined here possesses great theranostic potential for combined gene therapy and MRI diagnosis of HCC. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · Hepatology
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    ABSTRACT: 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 of tumor tissues 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.
    No preview · Article · Dec 2015 · Nanomedicine: nanotechnology, biology, and medicine
  • Du Cheng · Yong Wang · Hong Xiao · Zhen Wei Su · Jing Fang · Xingsu Yu · Xintao Shuai
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    ABSTRACT: 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.
    No preview · Article · Nov 2015 · Chemical Communications
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    ABSTRACT: 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.
    No preview · Article · Nov 2015 · Biomaterials
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    ABSTRACT: Novel diblock copolypeptides are synthesized and evaluated as a pH-sensitive drug delivery vector for anticancer drugs and siRNA co-delivery. The synthetic process involve the ring opening polymerization of α-amino acid N-carboxyanhydrides as well as aminolysis and deprotection reactions, and the structures are characterized. The copolypeptides can self-assemble into stable vesicles at neutral pH, and disassemble in acidic endosomal/lysosomal, which shown the pH-responsive behavior. The cell uptake results indicated that the vesicles can co-deliver DOX and siRNA inside the same cell and exhibit a pH-sensitive release behavior. Therefore, the novel polymeric vesicles are a promising carrier for co-delivery anticancer drug and siRNA to overcome the drug resistance and enhance cancer treatment. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    No preview · Article · Jul 2015 · Macromolecular Bioscience
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    ABSTRACT: Novel gold-shell nanoparticles (pH-GSNPs) are designed for the first time, which exhibit drug leakage-free behavior in a physiological environment, while achieving rapid drug release and remarkable aggregation for the nanogold interlayer of pH-GSNPs to shift their absorption to far-red and NIR as a photothermal agent in the intracellular microenvironment.
    No preview · Article · May 2015 · Chemical Communications
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    ABSTRACT: This study centers on the use of superparamagnetic iron oxide nanoparticles coated with polyethylene glycol-grafted polyethylenimine (PEG-g-PEI-SPION) as an MRI-visible and efficient nanovector for the gene modification and in vivo MRI tracking of rat bone marrow-derived mesenchymal stem cells (rBMSCs). PEG-g-PEI-SPION was first condensed with plasmid DNA to form nanoparticles, demonstrating low cytotoxicity and good biocompatibility for rBMSCs. Based on a reporter gene assay, PEG-g-PEI-SPION/pDNA had the highest transfection efficiency (62.6 ± 5.5%) in rBMSCs, which was significantly higher than that obtained using the cationic liposomes in lipofectamine 2000, a commercially available and worldwide used gene transfection agent, under the most optimal conditions (13.9 ± 2.6%; P
    No preview · Article · Apr 2015 · Journal of Biomedical Nanotechnology
  • Yuanyuan Yuan · Faming Gong · Yang Cao · Weicai Chen · Du Cheng · Xintao Shuai
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    ABSTRACT: The gene silencing activity of small interfering RNA (siRNA) has led to their use as tools for target validation and as potential therapeutics for a variety of diseases. A major challenge is the development of vectors with high delivery efficiency and low toxicity. Although poly(ethylenimine) (PEI) has been regarded as the most promising polymeric vector for nucleic acid delivery, the nonbiodegradable structure greatly hinders its clinical application. In the present study, a diblock copolymer, PEG-PAsp(DIP-DETA), of poly(ethylene glycol) (PEG) and poly(L-aspartic acid) (PAsp) randomly grafted with pH-sensitive 2-(diisopropylamino)ethylamine (DIP) and diethylenetriamine (DETA) groups was synthesized via ring-opening polymerization and aminolysis reaction. Similar to polyethylenimine (PEI), the copolymer possesses a multiamine structure that not only allows effective siRNA complexation at neutral pH but also facilitates lysosomal release of siRNA via a proton buffering effect. Moreover, the poly(L-aspartic acid) backbone renders the vector biodegradability, which is not achievable with PEI. This novel polymeric vector can mediate effective intracellular siRNA delivery in various cancer cells. Consequently, the delivery of BCL-2 siRNA resulted in target gene silencing, inducing apoptosis and inhibiting the growth of cancer cells. These results show the potential of this non-PEI based polymeric vector with proton buffering capacity and biodegradability for siRNA delivery in cancer therapy.
    No preview · Article · Apr 2015 · Journal of Biomedical Nanotechnology
  • Source
    Jin Wang · Linglan Ren · Jingguo Li · Jinsheng Huang · Du Cheng · Xintao Shuai
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    ABSTRACT: 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.
    Preview · Article · Feb 2015 · RSC Advances
  • Zhe Yang · Di Gao · Zhong Cao · Chao Zhang · Du Cheng · Jie Liu · Xintao Shuai
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    ABSTRACT: 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.
    No preview · Article · Feb 2015 · Biomaterials Science
  • Xintao Shuai · Du Cheng
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    ABSTRACT: This chapter summarizes the recent advances in stimulation-sensitive delivery systems. As the pH value of different microenvironments may vary in living body, pH-sensitive polymers have been employed as drug delivery systems, aiming at site-specific drug release. The ionization/deionization of the polymers depends on the pH value of the environment, which leads to the change of polymer solubility. Compared to cationic polymers, anionic polymers also undergo a solubility transformation at lower pH. Poly(propylene imine) (PPI) and poly(amidoamine) (PAMAM) are frequently used pH-sensitive dendrimers; PAMAM is biocompatible, nonimmunogenic, water-soluble, and terminal-modifiable. The volume phase transition of a thermo-sensitive polymer can be directly observed as the change in solubility is caused by the alterations in the way that the polymer chain interacts with solvent molecules. Along with the rapid development of nanomedicine, some other "intelligent" drug delivery systems have been designed to overcome the shortages of traditional nanocarriers.
    No preview · Article · Jan 2015
  • lu zhang · Hong Xiao · Jingguo Li · Du Cheng · Xintao Shuai
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    ABSTRACT: 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.
    No preview · Article · Jan 2015 · Nanoscale
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    ABSTRACT: A novel reduction and pH dual-sensitive nonviral vector for long-circulating and tumor-targeted siRNA delivery is described. The nanomedicine is negatively charged at neutral pH of bloodstream whereas positively charged at lower pH of tumor tissue (ca. 6.8). Interlayer crosslinking with disulfide bonds stabilizes the nanomedicine during blood circulation and allows quick intracellular siRNA release after endocytosis.
    No preview · Article · Dec 2014 · Advanced Materials
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    ABSTRACT: MSC's transplantation is a promising cell-based therapy for injuries in regenerative medicine, and in vivo visualization of transplanted MSCs with noninvasive technique is essential for the tracking of cell infusion and homing. A new cationic polymer, poly(ethylene glycol)-block-poly(l-aspartic acid)-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (PAI/SPION), was constructed as a magnetic resonance imaging (MRI)-visible non-viral vector for the delivery of plasmids DNA (pDNA) encoding for luciferase and red fluorescence protein (RFP) as reporter genes into MSCs. As a result, the MSCs were labeled with SPION and reporter genes. The PAI/SPION complexes exhibited high transfection efficiency in transferring pDNA into MSCs, which resulted in efficient luciferase and RFP co-expression. Furthermore, the complexes did not significantly affect the viability and multilineage differentiation capacity of MSCs. After the labeled MSCs were transplanted into the rats with acute liver injury via the superior mesenteric vein (SMV) injection, the migration behavior and organ-specific accumulation of the cells could be effectively monitored using the in vivo imaging system (IVIS) and MRI, respectively. The immunohistochemical analysis further confirmed that the transplanted MSCs were predominantly distributed in the liver parenchyma. Our results indicate that the PAI/SPION is a MRI-visible gene delivery agent which can effectively label MSCs to provide the basis for bimodal bioluminescence and MRI tracking in vivo.
    Full-text · Article · Sep 2014 · Biomaterials
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    ABSTRACT: 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.
    Preview · Article · Jul 2014
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    ABSTRACT: Drug resistance is a big problem in systemic chemotherapy of hepatocellular carcinoma (HCC), and nanomedicines loaded with both chemotherapeutic agents (e.g. paclitaxel, PTX) and siRNA's targeting antiapoptosis genes (e.g. BCL-2) possess the advantages to simultaneously overcome the efflux pump-mediated drug resistance and antiapoptosis-related drug resistance. However, tumor-penetrating drug delivery with this type of nanomedicines is extremely difficult due to their relatively big size compared to the single drug-loaded nanomedicines. Aiming at address this problem, US-responsive nanobubbles encapsulating both anti-cancer drug paclitaxel (PTX) and siRNA (PTX–NBs/siRNA) for HCC treatment were developed by hetero-assembly of polymeric micelles and liposomes in the present study. Utilizing an external low-frequency US force imposed to the tumor site, effective tumor-penetrating codelivery of siRNA and PTX was achieved via tail vein injection of PTX–NBs/siRNA into nude mice bearing human HepG2 xerografts. Consequently, the PTX treatment-inducible antiapoptosis in HepG2 cells was effectively suppressed by the codelivered siRNA targeting an antiapoptosis gene (BCL-2 siRNA) during chemotherapy. Owing to the synergistic anti-cancer effect of two therapeutic agents, tumor growth was completely inhibited using low-dose PTX in animal study. Our results highlight the great potential of this type of US-responsive hetero-assemblies carrying both anti-cancer drug and siRNA as an effective nanomedicinal system for HCC therapy.
    Full-text · Article · Jul 2014 · Biomaterials
  • Weicai Chen · Yuanyuan Yuan · Du Cheng · Jifeng Chen · Lu Wang · Xintao Shuai
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    ABSTRACT: Drug resistance is the greatest challenge in clinical cancer chemotherapy. Co-delivery of chemotherapeutic drugs and siRNA to tumor cells is a vital means to silence drug resistant genes during the course of cancer chemotherapy for an improved chemotherapeutic effect. This study aims at effective co-delivery of siRNA and anticancer drugs to tumor cells. A ternary block copolymer PEG-PAsp(AED)-PDPA consisting of pH-sensitive poly(2-(diisopropyl amino)ethyl methacrylate) (PDPA), reduction-sensitive poly(N-(2,2'-dithiobis(ethylamine)) aspartamide) PAsp(AED), and poly(ethylene glycol) (PEG) is synthesized and assembled into a core-shell structural micelle which encapsulated doxorubicin (DOX) in its pH-sensitive core and the siRNA-targeting anti-apoptosis BCL-2 gene (BCL-2 siRNA) in a reduction-sensitive interlayer. At the optimized size and zeta potential, the nanocarriers loaded with DOX and BCL-2 siRNA may effectively accumulate in the tumor site via blood circulation. Moreover, the dual stimuli-responsive design of micellar carriers allows microenviroment-specific rapid release of both DOX and BCL-2 siRNA inside acidic lysosomes with enriched reducing agent, glutathione (GSH, up to 10 mm). Consequently, the expression of anti-apoptotic BCL-2 protein induced by DOX treatment is significantly down-regulated, which results in synergistically enhanced apoptosis of human ovarian cancer SKOV-3 cells and thus dramatically inhibited tumor growth.
    No preview · Article · Jul 2014 · Small
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    ABSTRACT: MSC's transplantation is a promising cell-based therapy for injuries in regenerative medicine, and in vivo visualization of transplanted MSCs with noninvasive technique is essential for the tracking of cell infusion and homing. A new cationic polymer, poly(ethylene glycol)-block-poly(l-aspartic acid)-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles (PAI/SPION), was constructed as a magnetic resonance imaging (MRI)-visible non-viral vector for the delivery of plasmids DNA (pDNA) encoding for luciferase and red fluorescence protein (RFP) as reporter genes into MSCs. As a result, the MSCs were labeled with SPION and reporter genes. The PAI/SPION complexes exhibited high transfection efficiency in transferring pDNA into MSCs, which resulted in efficient luciferase and RFP co-expression. Furthermore, the complexes did not significantly affect the viability and multilineage differentiation capacity of MSCs. After the labeled MSCs were transplanted into the rats with acute liver injury via the superior mesenteric vein (SMV) injection, the migration behavior and organ-specific accumulation of the cells could be effectively monitored using the in vivo imaging system (IVIS) and MRI, respectively. The immunohistochemical analysis further confirmed that the transplanted MSCs were predominantly distributed in the liver parenchyma. Our results indicate that the PAI/SPION is a MRI-visible gene delivery agent which can effectively label MSCs to provide the basis for bimodal bioluminescence and MRI tracking in vivo.
    No preview · Article · Jun 2014 · Biomaterials
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    ABSTRACT: Background The triblock copolymers PEG-P(Asp-DIP)-P(Lys-Ca) (PEALCa) of polyethylene glycol (PEG), poly(N-(N’,N’-diisopropylaminoethyl) aspartamide) (P(Asp-DIP)), and poly (lysine-cholic acid) (P(Lys-Ca)) were synthesized as a pH-sensitive drug delivery system. In neutral aqueous environment such as physiological environment, PEALCa can self-assemble into stable vesicles with a size around 50-60 nm, avoid uptake by the reticuloendothelial system (RES), and encase the drug in the core. However, the PEALCa micelles disassemble and release drug rapidly in acidic environment that resembles lysosomal compartments. Methodology/Principal Findings The anticancer drug Paclitaxel (PTX) and hydrophilic superparamagnetic iron oxide (SPIO) were encapsulated inside the core of the PEALCa micelles and used for potential cancer therapy. Drug release study revealed that PTX in the micelles was released faster at pH 5.0 than at pH 7.4. Cell culture studies showed that the PTX-SPIO-PEALCa micelle was effectively internalized by human colon carcinoma cell line (LoVo cells), and PTX could be embedded inside lysosomal compartments. Moreover, the human colorectal carcinoma (CRC) LoVo cells delivery effect was verified in vivo by magnetic resonance imaging (MRI) and histology analysis. Consequently effective suppression of CRC LoVo cell growth was evaluated. Conclusions/Significance These results indicated that the PTX-SPION-loaded pH-sensitive micelles were a promising MRI-visible drug release system for colorectal cancer therapy.
    Full-text · Article · Jun 2014 · PLoS ONE

Publication Stats

4k Citations
552.77 Total Impact Points

Institutions

  • 2007-2015
    • Sun Yat-Sen University
      • Department of Chemical Engineering
      Shengcheng, Guangdong, China
  • 2012
    • Guangzhou Medical University
      Shengcheng, Guangdong, China
  • 2004-2006
    • Case Western Reserve University
      • Department of Biomedical Engineering
      Cleveland, Ohio, United States
  • 2003-2005
    • Philipps University of Marburg
      Marburg, Hesse, Germany
    • Technical Institute of Physics and Chemistry
      Peping, Beijing, China
  • 2001-2004
    • North Carolina State University
      • • Department of Materials Science and Engineering
      • • College of Textiles
      Raleigh, North Carolina, United States
  • 2000-2001
    • Tokyo Institute of Technology
      • Department of Biomolecular Engineering
      Edo, Tōkyō, Japan