A novel GSH-triggered polymeric nanomicelles for reversing MDR and enhancing antitumor efficiency of hydroxycamptothecin

Int J Pharm. 2021 May 1:600:120528. doi: 10.1016/j.ijpharm.2021.120528. Epub 2021 Mar 26.

Abstract

Tumor multidrug resistance (MDR) is one of the main reasons for the failure of clinical chemotherapy. Here, a bio-responsive anti-drug-resistant polymer micelle that can respond to the reductive GSH in the tumor microenvironment (TME) for delivery of HCPT was designed. A new type of polymer with anti-drug resistance and anti-tumor effect was synthesized and used to encapsulated HCPT to form reduction-sensitive micelles (PDSAH) by a thin-film dispersion method. It is demonstrated that the micelle formulation improves the anti-tumor activity and biosafety of HCPT, and also plays a significant role in reversing the drug resistance, which contributes to inhibiting the tumor growth and prolonging the survival time of H22 tumor-bearing mice. The results indicate that this nanoplatform can serve as a flexible and powerful system for delivery of other drugs that are tolerated by tumors or bacteria.

Keywords: HCPT; Multidrug resistance; Polymer inhibitor; Reduction sensitivity; Tumor targeting.

MeSH terms

  • Animals
  • Camptothecin* / analogs & derivatives
  • Cell Line, Tumor
  • Drug Delivery Systems
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Mice
  • Micelles*
  • Polymers

Substances

  • Micelles
  • Polymers
  • hydroxycamptothecinum
  • Camptothecin