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论文类型：期刊论文

发表时间：2019-05-20

发表刊物：Journal of biomaterials applications

收录刊物：PubMed

页面范围：885328219845081

ISSN号：1530-8022

关键字：ROS-responsive PEI-based polymers,Transfection efficiency,cytotoxicity,in vivo gene delivery,trigger-responsive degradation

摘要：The irreversible correlation between the transfection efficiency and cytotoxicity of polycations has always been the huge obstacle that severely limited the gene delivery efficiency. The undesired inconsistency could be mainly attributed to the molecular weight (MW) of the polycations, that is, polymers with high MW and positive charge densities exhibited enhanced transfection efficiency but with associated cytotoxicity. To address such critical challenge, we developed the degradable high MW polymers strategy which could condense DNA for the internalization and release DNA upon the trigger-responsive degradation. In this work, two kinds of degradable PEI-based polymers were prepared via the polyaddition of PEI600 and dienes with ester groups or thiol ketal groups. The PEI-based degradable polymers could efficiently condense plasmid DNA to form the nano-complexes with the size around 180 nm. They also exhibited improved gene delivery efficiency compared with commercial available transfection reagent, PEI25k, and were 380-520 folds higher than PEI600 in HeLa cells. The toxicity of the polymers could be reduced by the rapid degradation upon acid or ROS triggering as well as intracellular release of DNA and the cell viability could reach higher than 80% even at high doses. ROS-responsive PEI-based polymers also demonstrated its potential applications especially in cancer cells, which were proved by the enhanced in vivo gene expression in cancer cells. Our strategy therefore allows an effective tool to manipulate the relationship between transfection efficiency and cytotoxicity of polycations, and thus provides an effective insight into the rational design of non-viral gene delivery vectors.