Rongqin Huang

Fudan University, Shanghai, Shanghai Shi, China

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Publications (32)220.3 Total impact

  • Chengyi Li · Ying Meng · Shanshan Wang · Min Qian · Jianxin Wang · Weiyue Lu · Rongqin Huang ·
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    ABSTRACT: Multiple diagnosis of cancer by a facile fluorescent sensor is extremely attractive. Herein, a Cy3-labeled ssDNA probe (P0-Cy3) was π-π stacked on the surface of oxidized mesoporous carbon nanospheres (OMCN) to construct the fluorescent "turn-on" aptasensor. Attributing to the intrinsic properties of OMCN, the OMCN-based aptasensor can not only be used to detect mucin1 protein in liquid with a wide range of 0.1 - 10.6 μmol/L, a low detection limit of 6.52 nmol/L, and good selectivity, but also can quantify the cancer cells in solution with the linear range of 104 - 2 × 106 cells/mL and a detection limit of 8,500 cells/mL. Fascinatingly, this OMCN-based aptasensor was exploited to image cancer via solid tissues such as cells, tissue sections, ex vivo and in vivo tumors, in which the obvious distinguishability between cancer and normal tissues was clearly demonstrated. This is a robust and simple detection technique, which can well achieve the multiple diagnosis of cancer in vitro and in vivo.
    ACS Nano 11/2015; DOI:10.1021/acsnano.5b05137 · 12.88 Impact Factor
  • Yi Wang · Ying Meng · Shanshan Wang · Chengyi Li · Wei Shi · Jian Chen · Jianxin Wang · Rongqin Huang ·
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    ABSTRACT: Cancer imaging requires biocompatible and bright contrast-agents with selective and high accumulation in the tumor region but low uptake in normal tissues. Herein, 1-methyl-2-pyrrolidinone (NMP)-derived polymer-coated nitrogen-doped carbon nanodots (pN-CNDs) with a particle size in the range of 5-15 nm are prepared by a facile direct solvothermal reaction. The as-prepared pN-CNDs exhibit stable and adjustable fluorescence and excellent water solubility. Results of a cell viability test (CCK-8) and histology analysis both demonstrate that the pN-CNDs have no obvious cytotoxicity. Most importantly, the pN-CNDs can expediently enter glioma cells in vitro and also mediate glioma fluorescence imaging in vivo with good contrast via elevated passive targeting. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
    Small 03/2015; 11(29). DOI:10.1002/smll.201403718 · 8.37 Impact Factor
  • Kaiyuan Wang · Hui Yao · Ying Meng · Yi Wang · Xueying Yan · Rongqin Huang ·
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    ABSTRACT: Tumor-specific therapeutic platforms designed for combined tumor therapy has recently received wide attention. In this work, a new HB5 aptamer-functionalized mesoporous silica-carbon based doxorubicin (DOX)-loaded system (MSCN-PEG-HB5/DOX) was successfully constructed and characterized for chemo-photothermal combined therapy of human epithelial growth factor receptor 2 (HER2)-positive breast cancer cells. The in vitro release result showed that MSCN-PEG-HB5/DOX exhibited pH-sensitive and NIR-triggered release manner. HB5-modified nanoparticles showed significant higher cellular uptake in HER2-positive breast cancer cells (SK-BR-3) but not in normal breast epithelial cells (MCF-10A), compared to unmodified counterparts. The intracellular uptake of functional nanoparticles was mainly based on the receptor-mediated mechanism which was energy-dependent. Cytotoxicity experiments demonstrated that combined therapy induced highest cell killing effect compared to chemotherapy and photothermal therapy alone. The combination index (CI) was 0.253 indicating the synergistic effect of chemotherapy and photothermal therapy. These findings suggested that MSCN-PEG-HB5/DOX was a potential chemo-photothermal therapeutic platform targeting to HER2-positive breast cancers. Copyright © 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
    Acta Biomaterialia 01/2015; 16(1). DOI:10.1016/j.actbio.2015.01.002 · 6.03 Impact Factor
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    ABSTRACT: Successful glioma gene therapy lays on two important factors, the therapeutic genes and efficient delivery vehicles to cross the blood-brain barrier (BBB) and reach gliomas. In this work, a new gene vector was constructed based on dendrigraft poly-l-lysines (DGL) and polyethyleneglycol (PEG), conjugated with a cell-penetrating peptide, the nucleolar translocation signal (NoLS) sequence of the LIM Kinase 2 (LIMK2) protein (LIMK2 NoLS peptide, LNP), yielding DGL-PEG-LNP. Plasmid DNA encoding inhibitor of growth 4 (ING4) was applied as the therapeutic gene. DGL-PEG-LNP/DNA nanoparticles (NPs) were monodispersed, with a mean diameter of 90.6 ± 8.9 nm. The conjugation of LNP significantly enhanced the BBB-crossing efficiency, cellular uptake and gene expression within tumor cells. Mechanism studies suggested the involvement of energy, caveolae-mediated endocytosis and macropinocytosis in cellular uptake of LNP-modified NPs. MTT results showed that no apparent cytotoxicity was observed when cells were treated with synthesized vectors. Furthermore, LNP-modified NPs mediated strongest and most intensive apoptosis on the tumor site, and the longest median survival time of glioma-bearing mice. All the results demonstrated that LNP is a kind of efficient CPPs especially for BBB-crossing application, and DGL-PEG-LNP/DNA is a potential non-viral platform for glioma gene therapy via intravenous administration. Copyright © 2014 Elsevier Ltd. All rights reserved.
    Biomaterials 10/2014; 37C:345-352. DOI:10.1016/j.biomaterials.2014.10.034 · 8.56 Impact Factor
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    ABSTRACT: Tumor site-directed multifunctional therapeutic platforms such as photothermochemotherapy which respond to tumor-focused physical and biological stimuli are highly demanded for effective cancer therapy. Herein, targeting peptide-conjugated core-shell graphitic carbon@silica nanospheres with dual-ordered mesopores (MMPS) were successfully fabricated and developed as antitumoral doxorubicin (DOX) delivery system (MMPSD) for synergistic targeted photothermal chemotherapy of breast cancer. The hydrophilic mesoporous silica shell guarantees good water dispersity of MMPSD. The hydrophobic-graphitic mesoporous carbon core provides excellent hydrophobic drug loading, immediate contact between the drug and photothermal hotspots, and high NIR photothermal conversion efficiency. SP13 peptide facilitates MMPSD for targeted and enhanced delivery of DOX within HER2-positive SK-BR-3 breast cancer cells, while PEGylation ensures the biocompatibility. Thus, the MMPSD system exhibited efficient drug loading capacity, high targeting ability, sensitive NIR/pH-responsive DOX release, sustained release and excellent combined antitumor activity.
    ACS Nano 07/2014; 8(8). DOI:10.1021/nn5027214 · 12.88 Impact Factor
  • Yi Wang · Kaiyuan Wang · Xueying Yan · Rongqin Huang ·
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    ABSTRACT: A general strategy is developed for dual-triggered chemo-photothermal tumor therapy based on template semi-graphitized mesoporous silica nanoparticles (TsGMSN). The strategy endues classic MSN with new charming properties, while easily escaping from toxicity of the surfactant. The doxorubicin-loaded system (TsGMSND) exhibits synergistic heat-stimulative, pH-responsive, and sustained release, and effective combined tumor therapy.
    04/2014; 3(4). DOI:10.1002/adhm.201300324
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    ABSTRACT: Targeting peptide-modified magnetic graphene-based mesoporous silica (MGMSPI) are synthesized, characterized, and developed as a multifunctional theranostic platform. This system exhibits many merits, such as biocompatibility, high near-infrared photothermal heating, facile magnetic separation, large T2 relaxation rates (r2), and a high doxorubicin (DOX) loading capacity. In vitro and in vivo results demonstrate that DOX-loaded MGMSPI (MGMSPID) can integrate magnetic resonance imaging, dual-targeting recognition (magnetic targeting and receptor-mediated active targeting), and chemo-photothermal therapy into a single system for a visualized-synergistic therapy of glioma. In addition, it is observed that the MGMSPID system has heat-stimulated, pH-responsive, sustained release properties. All of these characteristics would provide a robust multifunctional theranostic platform for visualized glioma therapy.
    Small 01/2014; 10(1). DOI:10.1002/smll.201301297 · 8.37 Impact Factor
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    ABSTRACT: Purpose: To prepare an angiopep-conjugated dendrigraft poly-L-lysine (DGL)-based gene delivery system and evaluate the neuroprotective effects in the rotenone-induced chronic model of Parkinson's disease (PD). Methods: Angiopep was applied as a ligand specifically binding to low-density lipoprotein receptor-related protein (LRP) which is overexpressed on blood-brain barrier (BBB), and conjugated to biodegradable DGL via hydrophilic polyethyleneglycol (PEG), yielding DGL-PEG-angiopep (DPA). In vitro characterization was carried out. The neuroprotective effects were evaluated in a chronic parkinsonian model induced by rotenone using a regimen of multiple dosing intravenous administrations. Results: The successful synthesis of DPA was demonstrated via (1)H-NMR. After encapsulating the therapeutic gene encoding human glial cell line-derived neurotrophic factor (hGDNF), DPA/hGDNF NPs showed a sphere-like shape with the size of 119 ± 12 nm and zeta potential of 8.2 ± 0.7 mV. Angiopep-conjugated NPs exhibited higher cellular uptake and gene expression in brain cells compared to unmodified counterpart. The pharmacodynamic results showed that rats in the group with five injections of DPA/hGDNF NPs obtained best improved locomotor activity and apparent recovery of dopaminergic neurons compared to those in other groups. Conclusion: This work provides a practical non-viral gene vector for long-term gene therapy of chronic neurodegenerative disorders.
    Pharmaceutical Research 05/2013; 30(10). DOI:10.1007/s11095-013-1005-8 · 3.42 Impact Factor
  • Yi Wang · Kaiyuan Wang · Jianfeng Zhao · Xingang Liu · Juan Bu · Xueying Yan · Rongqin Huang ·
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    ABSTRACT: Current therapy of malignant glioma in clinic is unsatisfactory with poor patient compliance due to low therapeutic efficiency and strong systemic side effects. Herein, we combined chemo-photothermal targeted therapy of glioma within one novel multifunctional drug delivery system. A targeting peptide (IP)-modified mesoporous silica-coated graphene nanosheet (GSPI) was successfully synthesized and characterized, and first introduced to the drug delivery field. A doxorubicin (DOX)-loaded GSPI-based system (GSPID) showed heat-stimulative, pH-responsive, and sustained release properties. Cytotoxicity experiments demonstrated that combined therapy mediated the highest rate of death of glioma cells compared to that of single chemotherapy or photothermal therapy. Furthermore, the IP modification could significantly enhance the accumulation of GSPID within glioma cells. These findings provided an excellent drug delivery system for combined therapy of glioma due to the advanced chemo-photothermal synergistic targeted therapy and good drug release properties of GSPID, which could effectively avoid frequent and invasive dosing and improve patient compliance.
    Journal of the American Chemical Society 03/2013; 135(12). DOI:10.1021/ja312221g · 12.11 Impact Factor
  • Yi Wang · Wei Shi · Wenshuang Song · Li Wang · Xingang Liu · Jian Chen · Rongqin Huang ·
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    ABSTRACT: Receptor-mediated delivery of hydrophobic antitumor drugs is of great interest in chemotherapy of tumors such as glioma. Specific expression of interleukin-13 (IL-13) receptor has been characterized in glioma. In this work, a specific peptide corresponding to the residues within IL-13 protein, designated as IP, was exploited, for the first time, as a glioma-targeting ligand. IP was conjugated to mesoporous silica nanoparticles (MSN) via bifunctional polyethyleneglycol (PEG), constructing the vector MSN–PEG–IP. The successful synthesis of MSN–PEG–IP was demonstrated via Fourier transform infrared spectroscopy. The transmission electron microscopy result showed that the size of MSN–PEG–IP was about 160 nm with an average pore diameter of around 2.6 nm. The cellular uptake of doxorubicin (DOX)-loading IP-modified system (MSN–PEG–IP/DOX) was concentration-dependent in glioma U251 cells. IP modification could significantly enhance the cellular uptake of the drug delivery system in U251 cells but not in normal astrocyte 1800 cells, compared to unmodified counterparts. This effect was further verified by cytotoxicity analysis. Furthermore, the intracellular trafficking result indicated that the loaded DOX was mostly accumulated in nuclei, even at very short incubation time (5 min). All the results suggested that IP could be applied as a special glioma-targeting ligand, and MSN–PEG–IP is a potential vector for delivering hydrophobic chemotherapeutic drugs to IL-13 receptor-overexpressed tumors.
    Journal of Materials Chemistry 07/2012; 22(29):14608-14616. DOI:10.1039/C2JM32398B · 7.44 Impact Factor
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    ABSTRACT: The combination of gene therapy and chemotherapy is a promising treatment strategy for brain gliomas. In this paper, we designed a co-delivery system (DGDPT/pORF-hTRAIL) loading chemotherapeutic drug doxorubicin and gene agent pORF-hTRAIL, and with functions of pH-trigger and cancer targeting. Peptide HAIYPRH (T7), a transferrin receptor-specific peptide, was chosen as the ligand to target the co-delivery system to the tumor cells expressing transferrin receptors. T7-modified co-delivery system showed higher efficiency in cellular uptake and gene expression than unmodified co-delivery system in U87 MG cells, and accumulated in tumor more efficiently in vivo. DOX was covalently conjugated to carrier though pH-trigged hydrazone bond. In vitro incubation of the conjugates in buffers led to a fast DOX release at pH 5.0 (intracellular environment) while at pH 7.4 (blood) the conjugates are relatively stable. The combination treatment resulted in a synergistic growth inhibition (combination index, CI < 1) in U87 MG cells. The synergism effect of DGDPT/pORF-hTRAIL was verified in vitro and in vivo. In vivo anti-glioma efficacy study confirmed that DGDPT/pORF-hTRAIL displayed anti-glioma activity but was less toxic.
    Biomaterials 04/2012; 33(19):4907-16. DOI:10.1016/j.biomaterials.2012.03.031 · 8.56 Impact Factor
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    ABSTRACT: The choline transporter (ChT) is used to transport choline-derivate-modified nanoparticles across the blood-brain barrier. It is demonstrated that ChT is an ideal Trojan horse. The choline-derivate-modified nanoparticles exhibit higher permeability across the brain capillary endothelial cells (BCECs) monolayer in vitro and higher gene distribution and expression in vivo.
    Advanced Materials 10/2011; 23(39):4516-20. DOI:10.1002/adma.201101899 · 17.49 Impact Factor
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    ABSTRACT: Clinical diagnosis of cancers using magnetic resonance imaging (MRI) is highly dependent on contrast agents, especially for brain tumors which contain blood-brain barrier (BBB) at the early stage. However, currently mostly used low molecular weight contrast agents such as Gd-DTPA suffer from rapid renal clearance, non-specificity, and low contrast efficiency. The aim of this paper is to investigate the potential of a macromolecular MRI contrast agent based on dendrigraft poly-l-lysines (DGLs), using chlorotoxin (CTX) as a tumor-specific ligand. The contrast agent using CTX-modified conjugate as the main scaffold and Gd-DTPA as the payload was successfully synthesized. The results of fluorescent microscopy showed that the modification of CTX could markedly enhance the cellular uptake in C6 glioma and liver tumor cell lines, but not in normal cell line. Significantly increased accumulation of CTX-modified conjugate within glioma and liver tumor was further demonstrated in tumor-bearing nude mice using in vivo imaging system. The MRI results showed that the signal enhancement of mice treated with CTX-modified contrast reached peak level at 5 min for both glioma and liver tumor, 144.97% ± 19.54% and 158.69% ± 12.41%, respectively, significantly higher than that of unmodified counterpart and commercial control. And most importantly, the signal enhancement of CTX-modified contrast agent maintained much longer compared to that of controls, which might be useful for more exact diagnosis for tumors. CTX-modified dendrimer-based conjugate might be applied as an efficient MRI contrast agent for targeted and accurate tumor diagnosis. This finding is especially important for tumors such as brain glioma which is known hard to be diagnosed due to the presence of BBB.
    Biomaterials 08/2011; 32(22):5177-86. DOI:10.1016/j.biomaterials.2011.03.075 · 8.56 Impact Factor
  • Shixian Huang · Jianfeng Li · Liang Han · Shuhuan Liu · Haojun Ma · Rongqin Huang · Chen Jiang ·
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    ABSTRACT: Gene therapy offers a promising cure of brain glioma and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is able to induce cell apoptosis of glioma selectively without affecting the normal cells. In this study, the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), was selected as the principal vector. Angiopep-2, which can target to the low-density lipoprotein receptor-related protein-1 (LRP1) expressed on BCECs and glial cells, was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethyleneglycol (PEG) and then complexed with the DNA, designated as PAMAM-PEG-Angiopep/DNA nanoparticles (NPs). The cellular uptake mechanism explored in glial cells showed that the DNA of PAMAM-PEG-Angiopep/DNA NPs entered into the nuclei through the endosome/lysosome pathway. The in vivo biodistribution of PAMAM-PEG-Angiopep/DNA NPs in the brain especially the tumor site was higher than that of PAMAM-PEG/DNA NPs and PAMAM/DNA NPs. Furthermore, the TUNEL analysis showed a more wide-extended apoptosis in the PAMAM-PEG-Angiopep/pORF-TRAIL NPs treated group, compared to other groups including commercial Temozolomide-treated one. The median survival time of PAMAM-PEG-Angiopep/pORF-TRAIL NPs and Temozolomide treated on brain tumor-bearing mice was 61 and 49 days respectively, significantly longer than that of other groups. Besides, the NPs suggested low cytotoxicity after in vitro transfection. Thus, the results showed that Angiopep-2 could be exploited as a specific ligand to cross the BBB and targeted to glial cells, and PAMAM-PEG-Angiopep/DNA NPs can be a potential non-viral delivery system for gene therapy of glial tumor.
    Biomaterials 06/2011; 32(28):6832-8. DOI:10.1016/j.biomaterials.2011.05.064 · 8.56 Impact Factor
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    ABSTRACT: A tumor-targeting carrier, peptide HAIYPRH (T7)-conjugated polyethylene glycol-modified polyamidoamine dendrimer (PAMAM-PEG-T7) was explored to deliver magnetic resonance imaging (MRI) contrast agents targeting to the tumor cells specifically. Two different types of tumors, liver cancer and early brain glioma model (involved with the blood-brain barrier), were chosen to evaluate the imaging capacity of this contrast agent. PAMAM-PEG-T7 was synthesized, conjugated with diethylene triamine pentaacetic acid (DTPA) and further chelated gadolinium (Gd), yielding GdDTPA-PAMAM-PEG-T7. The result of ICP-AES showed that about 92 Gd ions could be loaded per PAMAM molecule. The calculated longitudinal relaxivity R1 of the GdDTPA-PAMAM-PEG-T7 was 10.7 mm(-1) S(-1) per Gd (984.4 mm(-1) S(-1) per PAMAM), while that of GdDTPA was only 4.8 mm(-1) S(-1). PAMAM-PEG-T7 had better targeting capacity to the liver cancer cells in vitro and in vivo, compared with PAMAM-PEG. The accumulation of PAMAM-PEG-T7 was 162.5% times that of PAMAM-PEG. But for glioma cells, PAMAM-PEG-T7 did not show its specificity. Furthermore, GdDTPA-PAMAM-PEG-T7 could improve the diagnostic efficiency of liver cancer with the enhanced signal (187%), compared to 130% for PAMAM-PEG and 121% for GdDTPA. GdDTPA-PAMAM-PEG-T7 could selectively identify liver cancer but not early glioma. This nanoscaled MRI contrast agent GdDTPA-PAMAM-PEG-T7 might allow for selective and efficient diagnosis of tumors without the natural barrier including liver cancer.
    Biomaterials 04/2011; 32(11):2989-98. DOI:10.1016/j.biomaterials.2011.01.005 · 8.56 Impact Factor
  • Rongqin Huang · Weilun Ke · Liang Han · Jianfeng Li · Shuhuan Liu · Chen Jiang ·
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    ABSTRACT: Gene therapy offers great potential for brain glioma. However, therapeutic genes could not reach glioma spontaneously. A glioma-targeting gene delivery system is highly desired to transfer exogenous genes throughout the tumor focus. In this study, the nanoscopic high-branching dendrimer, polyamidoamine (PAMAM), was selected as the main vector. Chlorotoxin (CTX), which has been demonstrated to bind specifically to receptor expressed in glioma, was exploited as the targeting ligand to conjugate PAMAM via bifunctional polyethyleneglycol (PEG), yielding PAMAM-PEG-CTX. The cellular uptake of CTX itself was observed apparently in C6 glioma cells, almost not in 293 cells. The modification of CTX could significantly increase the cellular uptake of vectors and the DNA-loaded nanoparticles (NPs) in C6 cells. The in vivo distribution of PAMAM-PEG-CTX/DNA NPs in the brain was higher than that of PAMAM/DNA NPs and PAMAM-PEG/DNA NPs. Furthermore, the gene expression of PAMAM-PEG-CTX/DNA NPs was higher and broader in glioma than that of unmodified and PEG-modified counterparts. The TUNEL analysis showed a more wide-extended apoptosis in the CTX-modified group, compared to other groups including commercial temozolomide group. The median survival time of CTX-modified group and temozolomide group was 59.5 and 49 days, respectively, significantly longer than that of other groups. The results suggested that CTX could be exploited as a special glioma-targeting ligand, and PAMAM-PEG-CTX/DNA NPs is a potential non-viral delivery system for gene therapy of glioma via intravenous administration.
    Biomaterials 03/2011; 32(9):2399-406. DOI:10.1016/j.biomaterials.2010.11.079 · 8.56 Impact Factor
  • Yang Liu · Rongqin Huang · Chen Jiang ·
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    ABSTRACT: The blood-brain barrier (BBB) exerts its central nervous system (CNS) protective function as it hinders the delivery of diagnostic and therapeutic agents to the brain. Gene therapy could be applied in conquering brain diseases such as neurodegenerative diseases and brain tumors by up- or down-regulating expression of diseased proteins. With the development of nanotechnology during the last thirty years, the nanocarriers for delivering drugs including gene medicines make it possible to transport drugs across the BBB. The nonviral nano-scaled gene delivery systems hold great promise for treating brain diseases due to their safety and convenience. Several brain targeting strategies, such as adsorptive- and receptor-mediated pathways have been developed to improve the brain targeting efficiency of non-viral gene delivery systems. In this review, the non-viral nanocarriers are focused for gene delivery and several possible strategies are discussed to achieve brain targeting effects. Finally, the applications of gene therapy in several brain diseases will be introduced.
    Current Nanoscience 01/2011; 7(1):55-70. DOI:10.2174/157341311794480309 · 1.10 Impact Factor
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    Liang Han · Rongqin Huang · Shuhuan Liu · Shixian Huang · Chen Jiang ·
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    ABSTRACT: The purpose of this work was to evaluate the potential of HAIYPRH (T7) peptide as a ligand for constructing tumor-targeting drug delivery systems. T7 could target to transferrin-receptor (TfR) through a cavity on the surface of TfR and then transport into cells via endocytosis with the help of transferrin (Tf). In this study, T7-conjugated poly(ethylene glycol) (PEG)-modified polyamidoamine dendrimer (PAMAM) (PAMAM-PEG-T7) was successfully synthesized and further loaded with doxorubicin (DOX), formulating PAMAM-PEG-T7/DOX nanoparticles (NPs). In vitro, almost 100% of DOX was released during 2 h in pH 5.5, while only 55% of DOX was released over 48 h in pH 7.4. The cellular uptake of DOX could be significantly enhanced when treated with T7-modified NPs in the presence of Tf. Also, the in vitro antitumor effect was enhanced markedly. The IC(50) of PAMAM-PEG-T7/DOX NPs with Tf was 231.5 nM, while that of NPs without Tf was 676.7 nM. T7-modified NPs could significantly enhance DOX accumulation in the tumor by approximately 1.7-fold compared to that of unmodified ones and by approximately 5.3-fold compared to that of free DOX. For in vivo antitumor studies, tumor growth of mice treated with PAMAM-PEG-T7/DOX NPs was significantly inhibited compared to that of mice treated with PAMAM-PEG/DOX NPs and saline. The study provides evidence that PAMAM-PEG-T7 can be applied as a potential tumor-targeting drug delivery system. T7 may be a promising ligand for targeted drug delivery to the tumor.
    Molecular Pharmaceutics 12/2010; 7(6):2156-65. DOI:10.1021/mp100185f · 4.38 Impact Factor
  • Liang Han · Rongqin Huang · Jianfeng Li · Shuhuan Liu · Shixian Huang · Chen Jiang ·
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    ABSTRACT: A combination cancer therapy was investigated via co-delivery of therapeutic gene encoding human tumor necrosis factor-related apoptosis-inducing ligand (pORF-hTRAIL) and doxorubicin (DOX) using a tumor-targeting carrier, peptide HAIYPRH (T7)-conjugated polyethylene glycol-modified polyamidoamine dendrimer (PAMAM-PEG-T7). T7, a transferrin receptor-specific peptide, was chosen as the ligand to target the co-delivery system to the tumor cells expressing transferrin receptors. The result of fluorescence scanning showed that about 375 DOX molecules were bound to one pORF-hTRAIL molecule. The co-delivery system was constructed based on the electrostatic interactions between pORF-hTRAIL-DOX complex and cationic PAMAM-PEG-T7. T7-modified co-delivery system showed higher efficiency in cellular uptake and gene expression than unmodified co-delivery system in human liver cancer Bel-7402 cells, and accumulated in tumor more efficiently in vivo. In comparison with single DOX or pORF-hTRAIL delivery system, co-delivery system induced apoptosis of tumor cells in vitro and inhibited tumor growth in vivo more efficiently. In mice bearing Bel-7402 xenografts, lower doses of co-delivery system (4 μg DOX/mouse, about 0.16 mg/kg) effectively inhibited tumor growth comparable to high doses (5 mg/kg) of free doxorubicin (77% versus 69%). These results suggested that T7-mediated co-delivery system of DOX and pORF-hTRAIL was a simply prepared, combined delivery platform which can significantly improve the anti-tumor effect. This co-delivery system might widen the therapeutic window and allow for the selective destruction of cancer cells.
    Biomaterials 10/2010; 32(4):1242-52. DOI:10.1016/j.biomaterials.2010.09.070 · 8.56 Impact Factor
  • Kun Shao · Rongqin Huang · Jianfeng Li · Liang Han · Liya Ye · Jinning Lou · Chen Jiang ·
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    ABSTRACT: Amphotericin B (AmB) is a poorly water soluble antibiotic and is used to treat fungal infections of the central nervous system (CNS). However, AmB shows poor penetration into the CNS. Angiopep-2, the ligand of low-density lipoprotein receptor-related protein (LRP) present on the BBB, exhibits higher transcytosis capacity and parenchymal accumulation, which allowed us to consider the selectivity of it for receptor-mediated drug targeting to the brain. With this in mind, we prepared angiopep-2 modified PE-PEG based micellar drug delivery system loaded with the antifungal drug AmB to evaluate the efficiency of AmB accumulating into the brain. PE-PEG based micelles as nano-scaled drug carriers were investigated by incorporating AmB with high drug entrapping efficiency, improving solubilization of AmB and reducing its toxicity to mammalian cells. The AmB-incorporated angiopep-2 modified micelles showed highest efficiency in penetrating across the blood-brain barrier (BBB) than unmodified micelles and Fungizone (deoxycholate amphotericin B) in vitro and in vivo. Meanwhile, contrary to the free Rho 123, the enhancement of Rho 123-incorporated angiopep-2 modified micelles across the BBB can be explained by angiopep-2 modified polymeric micelles that have a potential to overcome the activity of efflux proteins expressed on the BBB such as P-glycoprotein. In conclusion, angiopep-2 modified polymeric micelles could be developed as a novel drug delivery system for brain targeting.
    Journal of Controlled Release 10/2010; 147(1):118-26. DOI:10.1016/j.jconrel.2010.06.018 · 7.71 Impact Factor

Publication Stats

1k Citations
220.30 Total Impact Points


  • 2006-2015
    • Fudan University
      • • School of Pharmacy
      • • Department of Chemistry
      • • Department of Macromolecular Science
      Shanghai, Shanghai Shi, China