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Updated: Sep 26, 2025
Preparation and Characterization of Lipophilic Doxorubicin Pro-drug Micelles
Published on: August 2, 2016
pH/reduction dual-responsive hyaluronic acid-podophyllotoxin prodrug micelles for tumor targeted delivery
Min Li1, Yinan Zhao2, Jiao Sun2
1State Key Laboratory of Fine Chemicals, Dalian University of Technology, Dalian 116024, PR China; Key Laboratory of Biotechnology and Bioresources Utilization of Ministry of Education, Dalian Minzu University, Dalian 116600, PR China.
Abstract:
Polymer-based prodrug nanocarriers with tumor-targeting and controlled-release properties are in great demand for enhanced cancer treatment. Hyaluronic acid (HA), which has excellent biocompatibility and targeting ability for cluster determinant 44 (CD44), has been proposed for delivering drugs that have poor solubility and high toxicity. Herein, podophyllotoxin (PPT) was conjugated to HA via ester and disulfide linkages to construct a pH- and reduction-responsive prodrug (HA-S-S-PPT). The micelles self-assembled from HA-S-S-PPT prodrug efficiently accumulated at tumor site due to HA receptor-mediated endocytosis. HA-S-S-PPT micelles exhibited 33.1% higher cumulative release than HA-NH-CO-PPT micelles (sensitive only to pH) owing to their dual responsiveness to pH and reduction. HA-S-S-PPT micelles achieved excellent antitumor activity in vivo, with the tumor inhibition rate reaching 92%, significantly higher than that of HA-NH-CO-PPT micelles (65%), and negligible systemic toxicity. This controllable-targeting nanoparticle system provides a potential platform for clinical application of PPT.
