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Updated: Dec 24, 2025

Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
Published on: August 2, 2016
A reactive oxygen species-responsive prodrug micelle with efficient cellular uptake and excellent bioavailability
Long Xu1, Yidi Yang, Mingying Zhao
1National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610064, China. yjpu@scu.edu.cn.
Abstract:
Stimuli-responsive polymeric drug delivery systems are of great interest in anticancer research. Here, a reactive oxygen species (ROS)-responsive prodrug was prepared by thioketal linkage of poly(ethylene glycol) (PEG) and the anticancer drug doxorubicin (DOX). The ROS-responsive property of the prodrug was confirmed by dynamic light scattering and 1H NMR. The prodrug was then used as a drug carrier to further load DOX, to form a DOX-loaded prodrug micelle, which showed dual ROS and pH-responsive release behaviors. The prodrug micelle exhibited rapid intracellular uptake. Interestingly, the in vitro anticancer activity of the ROS-responsive prodrug micelle was better than that of the DOX-loaded prodrug micelle because of its faster cellular uptake and better bioavailability. However, both the ROS-responsive prodrug and drug-loaded prodrug micelles showed better anticancer efficacy than a non-responsive DOX-loaded poly(ethylene glycol)-block-polycaprolactone (PEG2k-PCL5k) micelle. Consistent results were obtained in in vivo animal experiments as the antitumor efficacy of the prodrug micelle was superior to that of the DOX-loaded prodrug micelle. Both micelles showed negligible systemic toxicity in vivo.
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