Chemosensitization and mitigation of Adriamycin-induced cardiotoxicity using combinational polymeric micelles for co-delivery of quercetin/resveratrol and resveratrol/curcumin in ovarian cancer

Nanomedicine. 2019 Jul:19:39-48. doi: 10.1016/j.nano.2019.03.011. Epub 2019 Apr 22.

Abstract

This work looks to improve the efficacy of Adriamycin (ADR) while mitigating its cardiotoxicity using combinations of micellar resveratrol (R): quercetin (Q) (mRQ) or R: curcumin (C) (mRC) in healthy mice and ovarian cancer xenograft models. Ovarian cancer cells, ES2-Luc, or A2780ADR are inoculated in mice (n =4/group) and sorted into eight cohorts. Mice are treated weekly for 4 weeks with ADR, ADR+mRQ, ADR+mRC, or controls (saline, empty micelles, ADR+EM, mRQ, or mRC). To evaluate the degree of cardioprotection, serum is collected to determine the cardiac Troponin I (cTnI). Cardiac tissue is collected for morphological evaluation and evaluation of creatine kinase levels. Our results indicate that mRQ+ADR is statistically significant in tumor reduction in xenograft models. In healthy mice, the left ventricular ejection fraction and fractional shortening in the ADR treated group is most compromised. Co-administration of mRQ with ADR can reduce ADR dosing through chemosensitization while being cardioprotective.

Keywords: Adriamycin; Cardioprotection; Chemosensitization; Micellar Polyphenols; Ovarian cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiotoxicity / diagnostic imaging
  • Cardiotoxicity / drug therapy*
  • Cardiotoxicity / physiopathology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Curcumin / administration & dosage
  • Curcumin / pharmacology
  • Curcumin / therapeutic use*
  • Doxorubicin / adverse effects*
  • Drug Delivery Systems
  • Female
  • Humans
  • Inhibitory Concentration 50
  • Luminescent Measurements
  • Mice
  • Micelles*
  • Ovarian Neoplasms / diagnostic imaging
  • Ovarian Neoplasms / drug therapy*
  • Polymers / chemistry*
  • Quercetin / administration & dosage
  • Quercetin / pharmacology
  • Quercetin / therapeutic use*
  • Resveratrol / administration & dosage
  • Resveratrol / pharmacology
  • Resveratrol / therapeutic use*
  • Stroke Volume / drug effects
  • Troponin I / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Micelles
  • Polymers
  • Troponin I
  • Doxorubicin
  • Quercetin
  • Curcumin
  • Resveratrol