聚乙二醇化
纳米载体
转染
基因传递
化学
胶束
乙二醇
生物物理学
脂质体
体内
内体
遗传增强
PEG比率
药物输送
细胞生物学
生物化学
聚乙二醇
细胞
基因
重组DNA
生物
生物技术
有机化学
物理化学
财务
水溶液
载体(分子生物学)
经济
作者
Xipeng Shen,Anjaneyulu Dirisala,Masahiro Toyoda,Yao Xiao,Hongbo Guo,Yuto Honda,Takahiro Nomoto,Hiroyuki Takemoto,Yutaka Miura,Nobuhiro Nishiyama
标识
DOI:10.1016/j.jconrel.2023.07.038
摘要
The success of gene therapy relies on gene nanocarriers to achieve therapeutic effects in vivo. Surface shielding of poly(ethylene glycol) (PEG), known as PEGylation, onto gene delivery carriers is a predominant strategy for extending blood circulation and improving therapeutic outcomes in vivo. Nevertheless, PEGylation frequently compromises the transfection efficiency by decreasing the interactions with the cellular membrane of the targeted cells, thereby preventing the cellular uptake and the subsequent endosomal escape. Herein, we developed a stepwise pH-responsive polyplex micelle for the plasmid DNA delivery with the surface covered by ethylenediamine-based polycarboxybetaines. This polyplex micelle switched its surface charge from neutral at pH 7.4 to positive at tumorous and endo-/lysosomal pH (i.e., pH 6.5 and 5.5, respectively), thus enhancing the cellular uptake and facilitating the endosomal escape toward efficient gene transfection. Additionally, the polyplex micelle demonstrated prolonged blood circulation as well as enhanced tumor accumulation, leading to highly effective tumor growth suppression by delivering an antiangiogenic gene. These results suggest the usefulness of a pH-responsive charge-switchable shell polymer on the surface of the polyplex micelle for the efficient nucleic acid delivery.
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