pH-responsive hybrid nanoparticle with enhanced dissociation characteristic for siRNA delivery

具有增强解离特性的 pH 响应性混合纳米粒子,用于 siRNA 递送

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作者:Menghao Shi, Xiufeng Zhao, Jiulong Zhang, Shuang Pan, Chunrong Yang, Ying Wei, Haiyang Hu, Mingxi Qiao, Dawei Chen, Xiuli Zhao

Conclusion

Taken all these together, PHD/LR was expected to be a suitable carrier for specific delivering siRNA for lung cancer therapy.

Methods

In this study, a novel triblock copolymer methoxy poly(ethylene glycol)-poly(histidine)-poly(sulfadimethoxine) (mPEG-PHis-PSD, shorten as PHD) was synthesized and used to construct novel nonviral gene vector with cationic liposomes.

Results

The resulting hybrid nanoparticles (PHD/LR) loaded with siPLK1 possessed excellent physiochemical properties. In vitro study indicated that PHD/LR could be efficiently internalized into human lung adenocarcinoma A549 cells and downregulated PLK1 protein expression to induce cell apoptosis, which was attributed to pH-induced instantaneous dissociation, efficient endo/lysosomal escape arose from PHD copolymer. Furthermore, in vivo antitumor activity demonstrated that PHD/LR could efficiently accumulated into tumor tissue and silenced PLK1 expression to possess antitumor activity.

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