Xintao Shuai

Sun Yat-Sen University, Shengcheng, Guangdong, China

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Publications (72)300.81 Total impact

  • [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 03/2014; · 7.82 Impact Factor
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    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; · 7.60 Impact Factor
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    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 01/2014; 9(3):e92050. · 3.73 Impact Factor
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    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; · 6.23 Impact Factor
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    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; · 6.93 Impact Factor
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    ABSTRACT: It is an emerging focus to explore a theranostic nanocarrier for simultaneous cancer imaging and therapy. Herein, we demonstrate a theranostic micelle system for cancer near infrared fluorescent (NIRF) imaging with enhanced signal to noise ratio and superior photothermal therapy. The copolymers consisting of monomethoxy poly(ethylene glycol) and alkylamine-grafted poly(l-aspartic acid) are assembled with carbocyanine dyes into theranostic micelles, which exhibit small size, high loading capacity, good stability, sustained release behavior, and enhanced cellular uptake. The micelles achieve the preferable biodistribution and long-term retention of carbocyanine dyes at tumor, which result in enhanced NIRF imaging by generating stable retention of NIRF signals at both hypervascular and hypovascular tumors during a long-term imaging period of up to 8 day, accompanying with negligible noise at normal tissues. The photostability of carbocyanine dye (Cypate) plays an important role for long-term cancer imaging with enhanced SNR. Moreover, the micelles exhibit severe photothermal damage on cancer cells via the destabilization of subcellular organelles upon photoirradiation, causing superior photothermal tumor regress. The micelles act as a powerful theranostic nanocarrier for simultaneous cancer imaging with high contrast and superior photothermal therapy.
    Biomaterials 09/2013; · 7.60 Impact Factor
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    ABSTRACT: Arsenic trioxide (As2O3) is a promising anticancer agent for solid tumors. However, the high toxicity to normal tissues resulting from the lack of tumor specificity remains a huge challenge in its systemic application. Targeted vectors enabling drug delivery to specific cancer cells bring about great potential for better therapeutic efficacy whereas low side effects in cancer treatments. Our previous work has demonstrated that the anti-CD44v6 single chain variable fragment (scFvCD44v6) screened out from the human phage-displayed scFv library possesses high specificity and affinity to membrane antigen CD44v6 over-expressing in a subset of epithelium-derived cancers, such as pancreatic, hepatocellular, colorectal and gastric cancers. Herein, a maleimide-functionalized amphiphilic diblock copolymer of poly (ethylene glycol) and poly (d, l-lactide) (mal-PEG-PDLLA) was synthesized and assembled to vesicles with arsenite ion (As) encapsulated in their cores (As-NPs). Conjugation of scFvCD44v6 with mal-PEG-PDLLA (scFv-As-NPs) enabled more efficient delivery of As and exhibited higher cytotoxic activity than non-targeted ones (As-NPs) in human pancreatic cancer cells PANC-1. Furthermore, the targeted delivery of As induced more significant gene suppression in terms of the expression of anti-apoptotic Bcl-2 protein. Consequently, the expression level of cleaved caspase-3 which is a molecular indicator of cell apoptosis was remarkably elevated. In animal tests, scFv-As-NPs were found to greatly increase accumulation of drug in tumor site and potentiate the efficacy of As in inhibiting tumor growth owing to the enhanced cell apoptosis. These results imply that our tumor specific nanocarriers provide a highly efficient and safe platform for pancreatic cancer therapy.
    Biomaterials 05/2013; · 7.60 Impact Factor
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    ABSTRACT: Ultrasound (US)-sensitive nanobubble (NB) which may utilize the physical power of US exposure to improve delivery efficiency to target cells is emerging as one of the most promising nanocarriers for drug delivery. On the basis of successfully fabricating NBs with the ability of passively accumulating in tumor tissue, in this study we synthesized a US-sensitive NB bearing siRNA (siRNA-NB) for tumor therapy via a hetero-assembling strategy using the siRNA-complexed polymeric micelles and gas-cored liposomes. The US exposure-aided siRNA transfection effectively enhanced the gene silencing effect of siRNA-NBs both in vitro and in vivo, which resulted in much elevated level of cancer cell apoptosis. Consequently, significantly improved therapeutic effect was achieved in a nude mouse glioma model, using siRNA-NBs bearing siRNA to target the anti-apoptosis gene sirtuin 2 (SIRT2). These results show that, with the aid of US exposure, the US-sensitive siRNA-NB may be an ideal delivery vector to mediate highly effective RNA interference for tumor treatment.
    Biomaterials 03/2013; · 7.60 Impact Factor
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    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 01/2013; 8(10):e76612. · 3.73 Impact Factor
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    ABSTRACT: 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 (SPION) 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 3rd 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 DGK-α gene. More excitingly, the therapeutic efficacy was readily monitored by non-invasive 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 non-invasive monitoring and a powerful nanomedicine platform for gene therapy of AR with high efficiency.
    ACS Nano 11/2012; · 12.06 Impact Factor
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    ABSTRACT: BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
    Journal of Gastroenterology 11/2012; · 3.79 Impact Factor
  • Xiangmin Miao, Liansheng Ling, Xintao Shuai
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    ABSTRACT: Dynamic light scattering based sensor for glucose was developed with oligonucleotide functionalized gold nanoparticles (Oligo-AuNPs). Oligonucleotide 5'-SH-(A)(12)-AGACAAGAGAGG-3' (Oligo 1) modified AuNPs and oligonucleotide 5'-CAACAGAGAACG-(A)(12)-HS-3' (Oligo 2) modified AuNPs could hybridize with oligonulceotide 5'-CGTTCTCTGTTGCCTCTCTTGTCT-3' (Oligo 3), which resulted in the aggregation of Oligo-AuNPs probes, and triggered the increase of their average diameter. However, Oligo 3 could be cleaved into DNA fragments by the mixture of glucose, glucose oxidase (GOD) and Fe(2+), and the DNA fragments could not hybridize with Oligo-AuNPs probes. Under the conditions of 3.7nM Oligo 1-AuNPs, 3.7nM Oligo 2-AuNPs, 8.0μg/mL GOD, 100nM Oligo 3 and 900nM Fe(2+), the average diameter of Oligo-AuNPs probes decreased linearly with the increasing concentration of glucose over the range from 50pmol/L to 5.0nmol/L, with a detection limit of 38pmol/L (3σ/slope). Moreover, five sugars had no effect on the average diameter of mixture of Oligo-AuNPs probes, GOD and Fe(2+), which demonstrated the good selectivity of the assay.
    Biosensors & bioelectronics 09/2012; · 5.43 Impact Factor
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    ABSTRACT: Copper ion (Cu(2+)) plays an important role in many biological reactions, and a suitable level of Cu(2+) is necessary for the regular metabolism of life. Thus developing a sensitive and simple method for determination of Cu(2+) is essential. Here, a novel and sensitive Cu(2+) sensor was developed based on detecting the average hydrodynamic diameter of AuNPs by using dynamic light scattering (DLS). Cu(2+)-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, Cu(2+) 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 Cu(2+) 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 Cu(2+) 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 Cu(2+) in water samples.
    The Analyst 05/2012; 137(13):3064-9. · 4.23 Impact Factor
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    ABSTRACT: Core/shell wormlike polymer brushes with densely grafted poly(ϵ-caprolactone)-b-poly(ethylene oxide) (PCL-b-PEO) are synthesized via grafting an alkynyl terminated PCL-b-PEO (ay-PCL(17) -b-PEO(113) ) onto a well-defined azido functionalized polymethacrylate (PGA(940) ) and are evaluated preliminarily as a single molecular cylindrical vehicle for drug delivery. Water soluble molecular worms of ca. 230 nm are obtained and then the anticancer drug doxorubicin (DOX) is loaded into its PCL core by hydrophobic interaction. Compared with spherical micelles from linear PCL(17) -b-PEO(113) , the brushes demonstrate a lower loading efficiency but a faster release rate of DOX. Confocal laser scanning microscopy measurements show that DOX-loaded cylindrical molecular brushes can easily enter into HeLa and HepG2 cells in 1 h.
    Macromolecular Rapid Communications 05/2012; 33(16):1351-5. · 4.93 Impact Factor
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    ABSTRACT: The therapeutic applications of neural stem cells (NSCs) have potential to promote recovery in many obstinate diseases in central nervous system. Regulation of certain gene expressions using siRNA may have significant influence on the fate of NSC. To achieve the optimum gene silencing effect of siRNA, non-viral vector polyethylene glycol-polyethyleneimine (PEG-PEI) was investigated in the delivery of siRNA to NSCs. The characteristics of PEG-PEI/siRNA polyplexes were detected by scanning electron microscopy (SEM). The effects of nanoparticles on cell viability were measured via CCK-8 assay. In addition, the transfection efficiency was evaluated by fluorescence microscope and flow cytometry, and real-time PCR and Western Blot were employed to detect the gene inhibition effect of siRNA delivered by PEG-PEI. The SEM micrographs showed that PEG-PEI could condense siRNA to form diffuse and spherical nanoparticles. The cytotoxicity of PEG-PEI/siRNA nanocomplexes (N/P=15) was significantly lower when compared with that of Lipofectamine 2000/siRNA (P<0.05). Moreover, the highest transfection efficiency of PEG-PEI/siRNA nanoparticles was obtained at an N/P ratio of 15, which was better than that achieved in the transfection using Lipofectamine 2000 (P<0.05). Finally, the gene knockdown effect of PEG-PEI/siRNA nanoparticles was verified at the levels of mRNA and protein. These results suggest that PEG-PEI may potentially be used as a siRNA delivery vector for neural regeneration therapy.
    Biochemical and Biophysical Research Communications 04/2012; 421(4):690-5. · 2.41 Impact Factor
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    ABSTRACT: 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.
    Polymer. 01/2012; 53(2):342–349.
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    ABSTRACT: The fabrication and initial applications of nanobubbles (NBs) have shown promising results in recent years. A small particle size is a basic requirement for ultrasound contrast-enhanced agents that penetrate tumor blood vessel pores to allow for targeted imaging and therapy. However, the nanoscale size of the particles used has the disadvantage of weakening the imaging ability of clinical diagnostic ultrasound. In this work, we fabricated a lipid NBs contrast-enhanced ultrasound agent and evaluated its passive targeting ability in vivo. The results showed that the NBs were small (436.8 ± 5.7 nm), and in vitro ultrasound imaging suggested that the ultrasonic imaging ability is comparable to that of microbubbles (MBs). In vivo experiments confirmed the ability of NBs to passively target tumor tissues. The NBs remained in the tumor area for a longer period because they exhibited enhanced permeability and retention. Direct evidence was obtained by direct observation of red fluorescence-dyed NBs in tumor tissue using confocal laser scanning microscopy. We have demonstrated the ability to fabricate NBs that can be used for the in vivo contrast-enhanced imaging of tumor tissue and that have potential for drug/gene delivery.
    International Journal of Nanomedicine 01/2012; 7:895-904. · 3.46 Impact Factor
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    ABSTRACT: An antibody-directed nonviral vector, polyethylene glycol-grafted polyethylenimine functionalized with superparamagnetic iron oxide nanoparticles and a gastric cancer-associated CD44v6 single-chain variable fragment (scFv(CD44v6),-PEG-g-PEI-SPION), was constructed as a gastric cancer-targeting and magnetic resonance imaging (MRI)-visible nanocarrier for small interfering RNA (siRNA) delivery. Biophysical characterization of PEG-g-PEI-SPION and scFv(CD44v6)-PEG-g-PEI-SPION was carried out, including siRNA condensation capacity, cell viability, and transfection efficiency. Both the targeting and nontargeting nanocarriers were effective for transferring siRNA in vitro. The cellular uptake and distribution of nanoparticles complexed with siRNA was analyzed by fluorescence imaging and immunofluorescent staining. Moreover, the gastric cancer-targeting effect was verified in vivo by MRI and histology analysis. These results indicate that scFv(CD44v6)-PEG-g-PEI-SPION is a promising nonviral vector for gastric cancer gene therapy and diagnosis.
    International Journal of Nanomedicine 01/2012; 7:359-68. · 3.46 Impact Factor
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    ABSTRACT: A folate conjugated ternary copolymer, FA-PEG-PEI-PCL, of poly(ethylene glycol) (PEG), poly(ethylene imine) (PEI), and poly(ɛ-caprolactone) (PCL) was synthesized. The copolymer self-assembled into cationic micelles capable of co-delivering siRNA and the anticancer drug doxorubicin (DOX). This dual functional nanocarrier demonstrated low cytotoxicity and high performance in drug/siRNA delivery. Upon the codelivery of siRNA, targeting the Bcl-2 gene, and DOX, using the folate-targeted nanocarrier, DOX-induced apoptosis in the skov-3 cells overexpressing folate receptor was significantly enhanced through a mechanism of downregulating the antiapoptotic protein Bcl-2, while simultaneously upregulating the proapoptotic protein Bax. This work suggested that the combination of Bcl-2 siRNA and DOX therapies is feasible, based on our dual functional nanocarrier, which set up a good basis for a future in vivo test.
    International Journal of Nanomedicine 01/2012; 7:3823-35. · 3.46 Impact Factor
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    ABSTRACT: Polyethylene glycol-grafted polyethylenimine (PEG-g-PEI) which was functionalized with a neuroblastoma cell-specific ligand, the GD2 single chain antibody (scAb(GD2)), was synthesized in order to effectively deliver Bcl-2 siRNA into neuroblastoma cells. This polymer was complexed first with superparamagnetic iron oxide nanoparticle (SPION) to get a MRI-visible targeted non-viral vector (scAb(GD2)-PEG-g-PEI-SPION) and then with Bcl-2 siRNA to form nanoparticles showing low cytotoxicity. The targeting capacity of scAb(GD2)-PEG-g-PEI-SPION was successfully verified in vivo and in vitro by magnetic resonance imaging. The single chain antibody encoded targeted polyplex was more effective in transferring Bcl-2 siRNA than the nontargeting one in SK-N-SH cells, a human neuroblastoma cell line, resulting in a 46.34% inhibition in the expression of Bcl-2 mRNA. Consequently, a high level of cell apoptosis up to 50.76% and a significant suppression of tumor growth were achieved, which indicates that scAb(GD2)-PEG-g-PEI-SPION is a promising magnetic resonance imaging-visible non-viral vector for targeted neuroblastoma siRNA therapy and diagnosis.
    International Journal of Nanomedicine 01/2012; 7:3319-32. · 3.46 Impact Factor

Publication Stats

925 Citations
338 Downloads
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300.81 Total Impact Points

Institutions

  • 2008–2014
    • Sun Yat-Sen University
      • • Department of Chemical Engineering
      • • Department of Oral Radiology
      Shengcheng, Guangdong, China
  • 2012
    • The Third People's Hospital
      Shen-ch’üan-shih, Zhejiang Sheng, China
    • Guangzhou Medical University
      Shengcheng, Guangdong, China
  • 2011
    • Sun Yat-Sen University of Medical Sciences
      Shengcheng, Guangdong, China
  • 2009–2011
    • Sichuan University
      • National Engineering Research Center for Biomaterials
      Chengdu, Sichuan Sheng, China
    • Sun Yat-Sen University Cancer Center
      Shengcheng, Guangdong, China
  • 2010
    • University of Wisconsin - Milwaukee
      • Department of Mechanical Engineering
      Milwaukee, WI, United States
  • 2001–2008
    • Tokyo Institute of Technology
      • Department of Biomolecular Engineering
      Tokyo, Tokyo-to, Japan
  • 2006
    • University of Texas Southwestern Medical Center
      • Simmons Comprehensive Cancer Center
      Dallas, TX, United States
  • 2004–2005
    • Case Western Reserve University
      • Department of Biomedical Engineering
      Cleveland, OH, United States
  • 2002–2004
    • North Carolina State University
      • Department of Materials Science and Engineering
      Raleigh, North Carolina, United States