Hypoxia-Activated\nPEGylated Paclitaxel Prodrug Nanoparticles\nfor Potentiated Chemotherapy

Abstract

Developing\ncontrolled drug-release systems is imperative and valuable\nfor increasing the therapeutic index. Herein, we synthesized hypoxia-responsive\nPEGylated (PEG = poly­(ethylene glycol)) paclitaxel prodrugs by utilizing\nazobenzene (Azo) as a cleavable linker. The as-fabricated prodrugs\ncould self-assemble into stable nanoparticles (PAP NPs) with high\ndrug content ranging from 26 to 44 wt %. The Azo group in PAP NPs\ncould be cleaved at the tumorous hypoxia microenvironment and promoted\nthe release of paclitaxel for exerting cytotoxicity toward cancer\ncells. In addition, comparative researches revealed that the PAP NPs\nwith the shorter methoxy-PEG chain (molecular weight = 750) possessed\nenhanced tumor suppression efficacy and alleviated off-target toxicity.\nOur work demonstrates a promising tactic to develop smart and simple\nnanomaterials for disease treatment.