Hypoxia-Activated PEGylated Paclitaxel Prodrug Nanoparticles for Potentiated Chemotherapy
Hypoxia-Activated PEGylated Paclitaxel Prodrug Nanoparticles for Potentiated Chemotherapy
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DOI：
10.1021/acsnano.2c05341
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发表时间：
2022-09-16
期刊：
影响因子：
17.1
通讯作者：
Xie, Zhigang
中科院分区：
文献类型：
--
作者：
Hao, Dengyuan;Meng, Qian;Xie, Zhigang
开发药物控释系统对提高治疗指标具有重要意义。本研究利用偶氮苯（Azo）作为可切割的连接体，合成了低氧反应的聚乙二醇化（PEG =聚乙二醇）紫杉醇前药。制备的前体药物可以自组装成稳定的纳米颗粒（PAP NPs），其药物含量在26%至44%之间。PAP NPs中的偶氮基团可在肿瘤缺氧微环境中被裂解，促进紫杉醇的释放，对癌细胞发挥细胞毒性。此外，对比研究表明，甲氧基- peg链较短（分子量= 750）的PAP NPs具有增强的抑瘤效果和减轻脱靶毒性。我们的工作展示了一种开发用于疾病治疗的智能和纳米材料的有前途的策略。
Developing controlled drug-release systems is imperative and valuable for increasing the therapeutic index. Herein, we synthesized hypoxia-responsive PEGylated (PEG = poly(ethylene glycol)) paclitaxel prodrugs by utilizing azobenzene (Azo) as a cleavable linker. The as-fabricated prodrugs could self-assemble into stable nanoparticles (PAP NPs) with high drug content ranging from 26 to 44 wt %. The Azo group in PAP NPs could be cleaved at the tumorous hypoxia microenvironment and promoted the release of paclitaxel for exerting cytotoxicity toward cancer cells. In addition, comparative researches revealed that the PAP NPs with the shorter methoxy-PEG chain (molecular weight = 750) possessed enhanced tumor suppression efficacy and alleviated off-target toxicity. Our work demonstrates a promising tactic to develop smart and nanomaterials for disease treatment.