转染
生物物理学
内化
赫拉
基因沉默
阳离子聚合
聚乙烯亚胺
乙二醇
材料科学
两亲性
内体
小干扰RNA
共聚物
分子生物学
化学
细胞内
细胞
生物化学
高分子化学
生物
有机化学
聚合物
基因
作者
Bin Xu,Yuyan Zhu,Cheng-Han Wang,Caian Qiu,Jing Sun,Yongyong Yan,Xin Chen,Jiancheng Wang,Qiang Zhang
标识
DOI:10.1021/acsami.8b04301
摘要
Here, the novel pH-responsive nanomicelles self-assembled with amphipathic meo-poly(ethylene glycol)-b-poly(l-histidine)-b-polyethylenimine (mPEG-b-PHis-b-PEI, EHE) copolymers based on hydrophobic interaction of PHis with deprotonation of imidazoles were developed for siRNA transfection. The cationic nanomicelles could electrostatically compact siRNA into stable EHE/siRNA nanoplexes with a hydrodynamic diameter of ∼190 nm and present a low toxicity in normal physiological condition (pH ∼ 7.4). Different from pH-irresponsive ECE/siRNA nanoplexes based on mPEG-b-poly(ε-caprolactone)-b-PEI (ECE), the EHE/siRNA nanoplexes exhibited a higher cellular uptake along with an increased ζ-potential (from +18 to +32 mV) when the pH changed from 7.4 to 6.8 (extracellular acidic microenvironments). After cell internalization, the EHE/siRNA nanoplexes also exhibited an enhanced nanostructural disassembling and release of siRNA from lysosomal acidic microenvironments (pH ∼ 5.5). Furthermore, it was demonstrated that the EHE/siEGFR nanoplexes downregulated the expression levels of the corresponding mRNA and protein more efficiently than ECE/siEGFR in HeLa cells. The improved siRNA silencing effects of EHE/siEGFR nanoplexes resulted from the higher cellular uptake and enhanced endosomal/lysosomal escape, which is associated with the pH-responsive disassembly of nanostructure as well as the synergistic “proton sponge” effects of PHis and PEI in EHE copolymers. Therefore, the pH-responsive EHE nanomicelles would be promising and potential carriers for cell transfection of siRNA.
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