Xintao Shuai

Sun Yat-Sen University, Shengcheng, Guangdong, China

Are you Xintao Shuai?

Claim your profile

Publications (96)485.25 Total impact

  • [Show abstract] [Hide abstract]
    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.
    Journal of Biomedical Nanotechnology 04/2015; 11(4). DOI:10.1166/jbn.2015.1966 · 7.58 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    RSC Advances 02/2015; 5(27). DOI:10.1039/C4RA16870D · 3.71 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    02/2015; DOI:10.1039/C4BM00369A
  • [Show abstract] [Hide abstract]
    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 0.05). More excitingly, the transplantation of rBMSCs modified by our MRI-visible vector complexed with a plasmid encoding human hepatocyte growth factor into fibrotic rat livers effectively restored albumin production and significantly suppressed transaminase activities. In addition, the transplanted rBMSCs displayed a sensitive signal on T 2/T*2-weighted images in vitro and in vivo, which enabled effective MRI tracking of the cells for up to 14 days post-transplantation. Although mesenchymal stem cells are well-known to be refractory in most of the current nonviral gene delivery techniques, our results demonstrate that the MRI-sensitive PEG-g-PEI-SPION is a highly efficient and readily observable nanovector for gene delivery into rBMSCs.
    Journal of Biomedical Nanotechnology 01/2015; 11(4). DOI:10.1166/jbn.2015.1967 · 7.58 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Advanced Materials 12/2014; 26(48). DOI:10.1002/adma.201403877 · 15.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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.
    Biomaterials 09/2014; 35(28):8249–8260. · 8.31 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    07/2014; 5(15). DOI:10.1039/C4PY00291A
  • Source
    [Show abstract] [Hide abstract]
    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.
    Biomaterials 07/2014; 35(22):5932–5943. DOI:10.1016/j.biomaterials.2014.03.072 · 8.31 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Small 07/2014; 10(13). DOI:10.1002/smll.201303951 · 7.51 Impact Factor
  • [Show abstract] [Hide abstract]
    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.
    Biomaterials 06/2014; DOI:10.1016/j.biomaterials.2014.06.014 · 8.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    PLoS ONE 06/2014; 9(6):e100732. DOI:10.1371/journal.pone.0100732 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 pK(a) 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.
    Polymer 06/2014; 55(15). DOI:10.1016/j.polymer.2014.05.038 · 3.77 Impact Factor
  • Source
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Resistance to chemotherapy and the side effects of anticancer drugs are the major obstacles for glioma treatment. The aim of the present study was to develop a novel approach for the treatment of gliomas that improved the therapeutic effect; the anticancer drug, doxorubicin (DOX), was combined with short interfering (si)RNA and monomethoxy polyethylene glycol polyethylenimine superparamagnetic iron oxide nanoparticle (mPEG-PEI-SPION), a magnetic resonance imaging (MRI)-visible nanoparticle. Specific siRNA molecules, delivered by mPEG-PEI-SPION, were employed to knockdown the PIN2-interacting protein 1 (PinX1) gene in C6 glioma cells. PinX1 is a nucleolar protein associated with telomere and telomerase. C6 cells were treated with DOX and/or PinX1-siRNA. The results of the transfection experiments revealed that siRNA/mPEG-PEI-SPION was transfected into C6 cells with high efficiency. PinX1-siRNA was unable to inhibit C6 cells, while in the PinX1-siRNA + DOX group, the same dose of DOX caused an increased loss of cell viability. Therefore, mPEG-PEI-SPION was shown to be viable for siRNA delivery into C6 cells and coadministration of DOX with PinX1-siRNA may be a potential therapeutic method for inhibiting gliomas.
    Experimental and therapeutic medicine 05/2014; 7(5):1170-1176. DOI:10.3892/etm.2014.1586 · 0.94 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rho-associated coiled-coil kinase 2 (ROCK2) is an attractive therapeutic target because it is overexpressed in many malignancies, including glioma. Therefore, we designed the current study to determine whether the downregulation of ROCK2 would sensitize the cytotoxic effect of temozolomide (TMZ) in U251 cells. Glycol-polyethyleneimine (PEG-PEI) was used to deliver siROCK2 to U251 cells, and the physical characteristics of the PEG-PEI/siROCK2 complex (referred to as the siROCK2 complex) were investigated. The transfection efficiency and cell uptake were determined by flow cytometry (FCM) and confocal laser microscopy (CLSM), respectively. U251 cells were then treated with 100 μM TMZ, siROCK2 complexes or their combination. The apoptosis rate and cell migration were measured by FCM and wound-healing assay, respectively. The levels of Bax, Bcl-2, cleaved caspase-3, MMP-2, and MMP-9 were detected to analyze the degrees of apoptosis and migration. Our results revealed that the characteristics of the siROCK2 complexes depended closely on the N/P ratios. PEG-PEI served as a good vector for siROCK2 and exhibited low cytotoxicity toward U251 cells. The CLSM assay showed that the siROCK2 complexes were successfully uptaken and that both the protein and mRNA levels of ROCK2 were significantly suppressed. Furthermore, the combination treatment induced a higher apoptosis rate and markedly increased the gap distance of U251 cells in the wound-healing assay. Levels of the proapoptotic proteins Bax and cleaved caspase-3 were significantly increased, whereas levels of the antiapoptotic protein Bcl-2 and the migration-related proteins MMP-2 and MMP-9 were significantly reduced by the combination treatment compared with either treatment alone. In conclusion, our results demonstrate that the combination of TMZ and siROCK2 effectively induces apoptosis and inhibits the migration of U251 cells. Therefore, the combination of TMZ and siROCK2 complex is a potential therapeutic approach for human glioma.
    PLoS ONE 03/2014; 9(3):e92050. DOI:10.1371/journal.pone.0092050 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stem cell therapies are promising strategies for the treatment of stroke. However, their clinical translation has not been fully realized due, in part, to insufficient ability to track stem cell migration and survival longitudinally over long periods of time in vivo. In this work, we synthesized a new class of manometer-sized cationic polymersomes loaded with superparamagnetic iron oxide nanoparticles and quantum dots for in vivo dual-modal imaging of stem cells. The results demonstrated that the synthesized cationic polymersomes can act as an effective and safety carrier to transfer image labels into neural stem cells, upon which the distribution and migration of grafted stem cells could be monitored by MR imaging up to 6 weeks and by fluorescence imaging within 4 weeks in the context of ischaemic brain injury. Cationic polymersomes hold great promise in the longitudinal monitoring of transplanted stem cells by using dual-modal MRI and optical imaging.
    Biomaterials 03/2014; DOI:10.1016/j.biomaterials.2014.02.042 · 8.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Folate-functionalized copolymers of poly(ethylene glycol) and 2-(diisopropylamino) ethylamine grafted poly(L-aspartic acid) are synthesized. The copolymers can self-assemble into nanoscaled micelles encapsulated with hydrophobic model drug Fluorescein Diacetate (FDA) and MRI diagnostic agents superparamagnetic iron oxide nanoparticles (SPIONs) in aqueous solution of a neutral pH resembling physiological environment, whereas disassemble in acidic endosomal/lysosomal compartments of tumor cells to achieve rapid drug release. In vitro drug release study showed that FDA release from the pH-sensitive micelles was much faster at pH 5.0 than at pH 7.4. Clustering of SPIONs inside the hydrophobic core of the micelles resulted in a high spin-spin (T2,) relaxivity for a super MRI sensitivity. Cell culture studies showed that the FDA-SPION-loaded micelles were effectively internalized by human hepatic Bel-7402 cancer cells following a folate receptor-mediated targeting mechanism, and then FDA was rapidly release from micelles inside lysosomal compartments. Micelles encapsulating paclitaxel (PTX) studies showed it can induce more effective cell toxicity. This study demonstrated the great potential of the pH-sensitive micelles as an effective multifunctional nanomedician platform for cancer therapy due to their active tumor targeting, pH-triggered drug release and ultrasensitive MRI responsiveness.
    Journal of Biomedical Nanotechnology 02/2014; 10(2):216-26. DOI:10.1166/jbn.2014.1729 · 7.58 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Nanoscale 12/2013; 6(3). DOI:10.1039/c3nr05024f · 6.74 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The neural ganglioside GD2 has recently been reported to be a novel surface marker that is only expressed on human bone marrow mesenchymal stem cells within normal marrow. In this study, an MRI-visible, targeted, non-viral vector for effective gene delivery to human bone marrow mesenchymal stem cells was first synthesized by attaching a targeting ligand, the GD2 single chain antibody (scAbGD2), to the distal ends of PEG-g-PEI-SPION. The targeted vector was then used to condense plasmid DNA to form nanoparticles showing stable small size, low cytotoxicity, and good biocompatibility. Based on a reporter gene assay, the transfection efficiency of targeting complex reached the highest value at 59.6% ± 4.5% in human bone marrow mesenchymal stem cells, which was higher than those obtained using nontargeting complex and lipofectamine/pDNA (17.7% ± 2.9% and 34.9% ± 3.6%, respectively) (P<0.01). Consequently, compared with the nontargeting group, more in vivo gene expression was observed in the fibrotic rat livers of the targeting group. Furthermore, the targeting capacity of scAbGD2-PEG-g-PEI-SPION was successfully verified in vitro by confocal laser scanning microscopy, Prussian blue staining, and magnetic resonance imaging. Our results indicate that scAbGD2-PEG-g-PEI-SPION is a promising MRI-visible non-viral vector for targeted gene delivery to human bone marrow mesenchymal stem cells.
    PLoS ONE 10/2013; 8(10):e76612. DOI:10.1371/journal.pone.0076612 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Nanomedicine: nanotechnology, biology, and medicine 09/2013; DOI:10.1016/j.nano.2013.08.007 · 5.98 Impact Factor

Publication Stats

3k Citations
485.25 Total Impact Points

Institutions

  • 2007–2015
    • Sun Yat-Sen University
      • • Department of Chemical Engineering
      • • Department of Biomedical Engineering
      Shengcheng, Guangdong, China
  • 2011
    • Sun Yat-Sen University of Medical Sciences
      Shengcheng, Guangdong, China
  • 2009
    • Sun Yat-Sen University Cancer Center
      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
  • 2002–2004
    • North Carolina State University
      • Department of Materials Science and Engineering
      Raleigh, North Carolina, United States
  • 2000–2002
    • Tokyo Institute of Technology
      • Department of Biomolecular Engineering
      Tokyo, Tokyo-to, Japan
  • 2001
    • Fayetteville State University
      Fayetteville, New York, United States
  • 1999
    • Polish Academy of Sciences
      • Center of Polymer and Carbon Materials
      Warszawa, Masovian Voivodeship, Poland
  • 1997
    • Beijing Institute Of Technology
      • Department of Energy Chemical Engineering
      Peping, Beijing, China