| Title | Self-assembly cationic nanoparticles based on cholesterol-grafted bioreducible poly(amidoamine) for siRNA delivery |
| Authors | Chen, Cheng-Jun Wang, Jian-Cheng Zhao, En-Yu Gao, Ling-Yan Feng, Qiang Liu, Xiao-Yan Zhao, Zhi-Xia Ma, Xiao-Fei Hou, Wen-Jie Zhang, Liang-Ren Lu, Wan-Liang Zhang, Qiang |
| Affiliation | Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. Peking Univ, Sch Pharmaceut Sci, Dept Pharmaceut, Beijing 100191, Peoples R China. |
| Keywords | Cholesterol-grafted bioreducible poly(amidoamine) Grafting degree Self-assembly cationic nanoparticle siRNA delivery Tumor therapy ENDOTHELIAL GROWTH-FACTOR GENE-TRANSFER PROPERTIES LUNG-CANCER CELLS DISULFIDE LINKAGES RNA INTERFERENCE AMINO-GROUPS CO-DELIVERY THERAPY TRANSFECTION POLYMERS |
| Issue Date | 2013 |
| Publisher | biomaterials |
| Citation | BIOMATERIALS.2013,34,(21),5303-5316. |
| Abstract | In this study, a series of bioreducible poly(amidoamine)s grafting different percentages of cholesterol (rPAA-Ch14: 14%, rPAA-Ch29: 29%, rPAA-Ch57: 57% and rPAA-Ch87: 87%) was synthesized and used for siRNA delivery. These amphiphilic polymers were able to self-assemble into cationic nanoparticles in aqueous solution at low concentrations. The nanoparticle formation was evidenced via cryo-transmission electron microscope (Cryo-TEM) and dynamic light scattering analysis. The average hydrodynamic size of rPAA-Ch blank nanoparticles was about 80-160 nm with zeta potential of 50 -60 mV. Also, the effects of different percentages of cholesterol grafted onto rPAA on physicochemical characteristics, in vitro cytotoxicity, cellular uptake, VEGF gene silencing efficacy and translocation mechanism of rPAA-Ch/siRNA complexes were investigated. The results showed that rPAA-Ch57 polymer was not only able to form stable nanocomplexes and possess high cell uptake, but also to exhibit the best in vitro VEGF gene silencing efficacy and the best in vivo tumor growth inhibition effect when it was formulated with VEGF-siRNA. Moreover, the observations of confocal laser scanning microscope (CLSM) and the study of cholesterol competitive inhibition demonstrated that endosomal/lysosomal escape and cytoplasmic dissociation of rPAA-Ch57/siRNA complexes were dependent on the "proton sponge effect" and disulfide cleavage, following internalization with cholesterol-related endocytosis pathway and subsequent transportion into endosomes/lysosomes. These findings indicated that the rPAA-Ch57 polymer should be a promising and potent carrier for siRNA delivery. (C) 2013 Elsevier Ltd. All rights reserved. |
| URI | http://hdl.handle.net/20.500.11897/156493 |
| ISSN | 0142-9612 |
| DOI | 10.1016/j.biomaterials.2013.03.056 |
| Indexed | SCI(E) EI PubMed |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
