du cheng - Academia.edu (original) (raw)
Papers by du cheng
Biomaterials
As the most fatal malignancy in brain, glioma cannot be effectively treated with the conventional... more As the most fatal malignancy in brain, glioma cannot be effectively treated with the conventional chemotherapy and thus techniques which may improve the chemotherapeutic effect are of great importance in clinical glioma treatment. Based on the folate-targeted multifunctional nanocarrier developed in our lab, effective co-delivery of DOX and siRNA into rat C6 glioma cells over-expressing folate receptors was achieved. Although cell apoptosis was initiated even at low DOX doses such as 0.5 μg/mL in the DOX-alone treatment mediated by the folate-targeted nanocarrier, anti-apoptotic response in C6 cells was activated as well, as revealed by molecular biological investigations. Delivery of BCL-2 siRNA using the folate-targeted nanocarrier can effectively suppress the anti-apoptotic response and sensitized C6 cells to DOX treatment both in vitro and in vivo. In particular, animal studies using the in situ rat C6 glioma model showed that the folate-targeted co-delivery of BCL-2 siRNA and DOX caused not only an obvious down-regulation of the anti-apoptotic BCL-2 gene but also a remarkable up-regulation of the pro-apoptotic Bax gene, resulting in the significantly elevated level of caspase-3 activation and remarkable cell apoptosis in tumor tissues. Our results strongly demonstrated the synergistic effect of siRNA and DOX in inducing glioma C6 cell apoptosis, upon which an excellent therapeutic effect was achieved using the folate-targeted co-delivery strategy as indicated by the effective tumor growth inhibition and prolonged rat survival time in the animal test.
Biomaterials, 2011
Diblock copolymers (PEI-PCL) of poly(e-caprolactone) (PCL) and linear poly(ethylene imine) (PEI) ... more Diblock copolymers (PEI-PCL) of poly(e-caprolactone) (PCL) and linear poly(ethylene imine) (PEI) were synthesized and assembled to biodegradable nano-carriers for co-delivery of BCL-2 siRNA and doxorubicin (DOX). Folic acid as a tumor-targeting ligand was conjugated to the polyanion, poly(ethylene glycol)-block-poly(glutamic acid) (FA-PEG-PGA). Driven by the electrostatic interaction, FA-PEG-PGA was coated onto the surface of the cationic PEI-PCL nanoparticles pre-loaded with siRNA and DOX, potentiating a ligand-directed delivery to human hepatic cancer cells Bel-7402. At certain N/P and C/N ratios (N/P: PEI-PCL nitrogen to siRNA phosphate; C/N: FA-PEG-PGA carboxyl to PEI-PCL amine), the nanoparticles exhibited not only high transfection efficiency but also ideally controlled release of drug. Compared to non-specific delivery, the folate-targeted delivery of BCL-2 siRNA resulted in more significant gene suppression at both the BCL-2 mRNA and protein expression levels, inducing cancer cell apoptosis and improving the therapeutic efficacy of the co-administered DOX. Herein we demonstrated that co-loading siRNA and small molecular drug in a multifunctional hierarchical nano-assembly enabled simultaneously delivering siRNA and drug into the same cancer cells, yielding synergistic effect of RNA interference and chemotherapy in cancer.
Biomaterials, 2011
A major challenge in gene therapy is the development of effective gene delivery vectors with low ... more A major challenge in gene therapy is the development of effective gene delivery vectors with low toxicity. In the present study, linear poly(ethylenimine) (lPEI) with low molecular weight was grafted onto the block copolymer (PPL) of poly(L-lysine) (PLL) and poly(ethylene glycol)(PEG), yielding a ternary copolymer PEG-b-PLL-g-lPEI (PPI) for gene delivery. In such molecular design, PLL, lPEI and PEG blocks were expected to render the vector biodegradability, proton buffering capacity, low cationic toxicity and potentially long circulation in vivo, respectively. Given proper control of molecular composition, the copolymers demonstrated lower cytotoxicity, proton buffering capacity, ability to condense pDNA and mediate effective gene transfection in various cell lines. With folate as an exemplary targeting ligand, the FA-PPI/pDNA complex showed much higher transgene activity than its nontargeting counterpart for both reporter and therapeutic genes in folate receptor(FR)-positive cells. FA-PPI mediated effective transfection of the TNF-related apoptosis-inducing ligand gene (TRAIL) in human hepatoma Bel 7402 cells, leading to cell apoptosis and great suppression of cell viability. Our results indicate that the copolymers might be a promising vector combining low cytotoxicity, biodegradability, and high gene transfection efficiency.
Frontiers of Materials Science in China, 2009
A new composite brake material was fabricated with metallic powders, barium sulphate and modified... more A new composite brake material was fabricated with metallic powders, barium sulphate and modified phenolic resin as the matrix and carbon fiber as the reinforced material. The friction, wear and fade characteristics of this composite were determined using a D-MS friction material testing machine. The surface structure of carbon fiber reinforced friction materials was analyzed by scanning electronic microscopy (SEM). Glass fiberreinforced and asbestos fiber-reinforced composites with the same matrix were also fabricated for comparison. The carbon fiber-reinforced friction materials (CFRFM) shows lower wear rate than those of glass fiber- and asbestos fiber-reinforced composites in the temperature range of 100°C-300°C. It is interesting that the frictional coefficient of the carbon fiber-reinforced friction materials increases as frictional temperature increases from 100°C to 300°C, while the frictional coefficients of the other two composites decrease during the increasing temperatures. Based on the SEM observation, the wear mechanism of CFRFM at low temperatures included fiber thinning and pull-out. At high temperature, the phenolic matrix was degraded and more pull-out enhanced fiber was demonstrated. The properties of carbon fiber may be the main reason that the CFRFM possess excellent tribological performances.
Chinese Physics Letters, 2011
Biomaterials
As the most fatal malignancy in brain, glioma cannot be effectively treated with the conventional... more As the most fatal malignancy in brain, glioma cannot be effectively treated with the conventional chemotherapy and thus techniques which may improve the chemotherapeutic effect are of great importance in clinical glioma treatment. Based on the folate-targeted multifunctional nanocarrier developed in our lab, effective co-delivery of DOX and siRNA into rat C6 glioma cells over-expressing folate receptors was achieved. Although cell apoptosis was initiated even at low DOX doses such as 0.5 μg/mL in the DOX-alone treatment mediated by the folate-targeted nanocarrier, anti-apoptotic response in C6 cells was activated as well, as revealed by molecular biological investigations. Delivery of BCL-2 siRNA using the folate-targeted nanocarrier can effectively suppress the anti-apoptotic response and sensitized C6 cells to DOX treatment both in vitro and in vivo. In particular, animal studies using the in situ rat C6 glioma model showed that the folate-targeted co-delivery of BCL-2 siRNA and DOX caused not only an obvious down-regulation of the anti-apoptotic BCL-2 gene but also a remarkable up-regulation of the pro-apoptotic Bax gene, resulting in the significantly elevated level of caspase-3 activation and remarkable cell apoptosis in tumor tissues. Our results strongly demonstrated the synergistic effect of siRNA and DOX in inducing glioma C6 cell apoptosis, upon which an excellent therapeutic effect was achieved using the folate-targeted co-delivery strategy as indicated by the effective tumor growth inhibition and prolonged rat survival time in the animal test.
Biomaterials, 2011
Diblock copolymers (PEI-PCL) of poly(e-caprolactone) (PCL) and linear poly(ethylene imine) (PEI) ... more Diblock copolymers (PEI-PCL) of poly(e-caprolactone) (PCL) and linear poly(ethylene imine) (PEI) were synthesized and assembled to biodegradable nano-carriers for co-delivery of BCL-2 siRNA and doxorubicin (DOX). Folic acid as a tumor-targeting ligand was conjugated to the polyanion, poly(ethylene glycol)-block-poly(glutamic acid) (FA-PEG-PGA). Driven by the electrostatic interaction, FA-PEG-PGA was coated onto the surface of the cationic PEI-PCL nanoparticles pre-loaded with siRNA and DOX, potentiating a ligand-directed delivery to human hepatic cancer cells Bel-7402. At certain N/P and C/N ratios (N/P: PEI-PCL nitrogen to siRNA phosphate; C/N: FA-PEG-PGA carboxyl to PEI-PCL amine), the nanoparticles exhibited not only high transfection efficiency but also ideally controlled release of drug. Compared to non-specific delivery, the folate-targeted delivery of BCL-2 siRNA resulted in more significant gene suppression at both the BCL-2 mRNA and protein expression levels, inducing cancer cell apoptosis and improving the therapeutic efficacy of the co-administered DOX. Herein we demonstrated that co-loading siRNA and small molecular drug in a multifunctional hierarchical nano-assembly enabled simultaneously delivering siRNA and drug into the same cancer cells, yielding synergistic effect of RNA interference and chemotherapy in cancer.
Biomaterials, 2011
A major challenge in gene therapy is the development of effective gene delivery vectors with low ... more A major challenge in gene therapy is the development of effective gene delivery vectors with low toxicity. In the present study, linear poly(ethylenimine) (lPEI) with low molecular weight was grafted onto the block copolymer (PPL) of poly(L-lysine) (PLL) and poly(ethylene glycol)(PEG), yielding a ternary copolymer PEG-b-PLL-g-lPEI (PPI) for gene delivery. In such molecular design, PLL, lPEI and PEG blocks were expected to render the vector biodegradability, proton buffering capacity, low cationic toxicity and potentially long circulation in vivo, respectively. Given proper control of molecular composition, the copolymers demonstrated lower cytotoxicity, proton buffering capacity, ability to condense pDNA and mediate effective gene transfection in various cell lines. With folate as an exemplary targeting ligand, the FA-PPI/pDNA complex showed much higher transgene activity than its nontargeting counterpart for both reporter and therapeutic genes in folate receptor(FR)-positive cells. FA-PPI mediated effective transfection of the TNF-related apoptosis-inducing ligand gene (TRAIL) in human hepatoma Bel 7402 cells, leading to cell apoptosis and great suppression of cell viability. Our results indicate that the copolymers might be a promising vector combining low cytotoxicity, biodegradability, and high gene transfection efficiency.
Frontiers of Materials Science in China, 2009
A new composite brake material was fabricated with metallic powders, barium sulphate and modified... more A new composite brake material was fabricated with metallic powders, barium sulphate and modified phenolic resin as the matrix and carbon fiber as the reinforced material. The friction, wear and fade characteristics of this composite were determined using a D-MS friction material testing machine. The surface structure of carbon fiber reinforced friction materials was analyzed by scanning electronic microscopy (SEM). Glass fiberreinforced and asbestos fiber-reinforced composites with the same matrix were also fabricated for comparison. The carbon fiber-reinforced friction materials (CFRFM) shows lower wear rate than those of glass fiber- and asbestos fiber-reinforced composites in the temperature range of 100°C-300°C. It is interesting that the frictional coefficient of the carbon fiber-reinforced friction materials increases as frictional temperature increases from 100°C to 300°C, while the frictional coefficients of the other two composites decrease during the increasing temperatures. Based on the SEM observation, the wear mechanism of CFRFM at low temperatures included fiber thinning and pull-out. At high temperature, the phenolic matrix was degraded and more pull-out enhanced fiber was demonstrated. The properties of carbon fiber may be the main reason that the CFRFM possess excellent tribological performances.
Chinese Physics Letters, 2011