PH-sensitive hydroxyethyl starch-doxorubicin conjugates as antitumor prodrugs with enhanced anticancer efficacy

Yu Zhu, Xuemei Yao, Xiaofei Chen, Li Chen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

Doxorubicin (DOX) is a widely used chemotherapeutic drug for the treatment of several types of cancers, which has limitation in clinical applications because of severe heart toxicity. Herein, to reduce the fast clearance from the blood system and the severe systemic toxicity caused by the nonspecific protein adsorption, a pH-sensitive drug delivery system with higher drug conjugated content was prepared by conjugating DOX onto hydroxyethyl starch (HES) with a pH-sensitive hydrazone bond. In normal physiological environment, the release of DOX conjugated onto HES was slight which could be neglected without any side effect. However, in an acidic environment mimicking the tumor microenvironment, this pH-sensitive hydrazone linkage provided a controlled and sustained release of DOX over a period of more than 3 days. The conjugates had good biocompatibility, long circulation, and lower cytotoxicity, which could efficiently be transferred into HeLa and HepG2 cells and release the conjugated drug. Based on these promising properties, these HES-DOX conjugates outline the significant potential for future biomedical application in the controlled release of antitumor drugs.

Original languageEnglish
Article number42778
JournalJournal of Applied Polymer Science
Volume132
Issue number45
DOIs
Publication statusPublished - 1 Dec 2015
Externally publishedYes

Keywords

  • Biomaterials
  • Drug delivery systems
  • Stimuli-sensitive polymers

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