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Stepwise dual pH and redox-responsive cross-linked polypeptide nanoparticles for enhanced cellular uptake and effective cancer therapy
时间:2023-02-23 16:21:55
作品信息

期刊

Journal of Materials Chemistry B

标题

Stepwise dual pH and redox-responsive cross-linked polypeptide nanoparticles for enhanced cellular uptake and effective cancer therapy

作者

Jing Qu, Rui Wang, Si Peng, Mengyao Shi, Sheng-Tao Yang, Jian-bin Luo, Juan Lin and  Qing-han Zhou

摘要

The systemic toxicity, reduced cellular internalization, and uncontrollable intracellular drug release of smart nanoparticles (NPs) still need to be overcome for effective cancer therapy. Herein, a series of stepwise dual pH and redox responsive cross-linked polypeptides based on poly(L-lysine-co-N,N-bis(acryloyl)cystamine-co-γ-glutamic acid) (PLBG), were prepared for enhanced cellular uptake and effective cancer therapy. The prepared cross-linked PLBG nanoparticles (PLBG-NPs) exhibit negatively charged surfaces under physiological conditions, and the surface charge of the PLBG-NPs was observed to switch from negative to positive in a slightly acidic tumor extracellular environment at a pH level of ∼6.5. Finally, the endosome escape of the PLBG-NPs was facilitated via a “proton-sponge” effect via protonation of the polymer chain in the endo/lysosome environment of the tumor cell at a pH level of ∼5.0. Moreover, rapid drug release was triggered by a high concentration of reducing glutathione (GSH) in tumor cells via destruction of the disulfide linkages in the PLBG-NPs. Cytotoxicity assays demonstrated that no noticeable cytotoxicity was observed for the PLBG-NPs. However, DOX-loaded PLBG-NPs (PLBG-NPs-DOX) demonstrated remarkable tumor cell killing effects. In HeLa tumor-bearing mice, PLBG-NPs-DOX showed sustained tumor accumulation and enhanced inhibitory effects on tumor growth and angiogenesis. In conclusion, it is suggested that the as-designed novel charge-conversion PLBG-NPs with stepwise pH-responsivity and biodegradability could be used as a potential drug carrier for effective cancer therapy with less systemic toxicity.

原文链接

https://pubs.rsc.org/en/content/articlelanding/2019/tb/c9tb01773a

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