Co-delivery of doxorubicin and quercetin via mPEG–PLGA copolymer assembly for synergistic anti-tumor efficacy and reducing cardio-toxicity

Waseem Akhtar Qureshi, Ruifang Zhao, Hai Wang, Tianjiao Ji, Yanping Ding, Ayesha Ihsan, Ayeesha Mujeeb, Guangjun Nie, Yuliang Zhao

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Quercetin (Que) is a natural multifunctional bioflavonoid, and has shown great potential for reducing adverse side effects and enhancing anti-tumor efficacy of chemotherapeutic drugs. However, its clinical application is limited due to very low solubility and structural instability in physiological systems. Herein, we co-delivered hydrophobic quercetin and hydrophilic doxorubicin (Dox) by developing a biocompatible nanocarrier comprising of an amphiphilic polymer, methoxy poly(ethylene glycol) and poly(D, L-lactide-co-glycolide), respectively. The anti-tumor and prophylactic efficacy of this system was evaluated in cellular and animal models. Our findings illustrated that the Dox-Que nanoparticulate formulation protected normal vascular endothelial cells from either free or nanoparticulate doxorubicin-induced cytotoxicity and increased cancer cell death. Compared with free doxorubicin and its nanoformulation, co-delivery of quercetin and doxorubicin using our nanosystem synergistically inhibited tumor growth, while maintaining normal levels of cardiac function indicators in serum and recovering the histopathological damages in heart tissue. This study demonstrates a promising strategy for enhancing anti-cancer drug efficacy and reducing nanoparticulate chemotherapy-induced toxicity on normal tissues.

Original languageEnglish (US)
Pages (from-to)1689-1698
Number of pages10
JournalScience Bulletin
Volume61
Issue number21
DOIs
StatePublished - Nov 1 2016

Keywords

  • Cancer therapy
  • Cardio-toxicity
  • Doxorubicin
  • Polymeric nanoparticles
  • Quercetin

ASJC Scopus subject areas

  • General

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