TitleChemosensitization and mitigation of Adriamycin-induced cardiotoxicity using combinational polymeric micelles for co-delivery of quercetin/resveratrol and resveratrol/curcumin in ovarian cancer.
Publication TypeJournal Article
Year of Publication2019
AuthorsFatease, AAl, Shah, V, Nguyen, DX, Cote, B, LeBlanc, N, Rao, DA, Alani, AWG
JournalNanomedicine
Volume19
Pagination39-48
Date Published2019 07
ISSN1549-9642
KeywordsAnimals, Apoptosis, Cardiotoxicity, Cell Line, Tumor, Cell Survival, Curcumin, Doxorubicin, Drug Delivery Systems, Female, Humans, Inhibitory Concentration 50, Luminescent Measurements, Mice, Micelles, Ovarian Neoplasms, Polymers, Quercetin, Resveratrol, Stroke Volume, Troponin I, Xenograft Model Antitumor Assays
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.
DOI10.1016/j.nano.2019.03.011
Alternate JournalNanomedicine
PubMed ID31022465
Grant ListR15 CA227754 / CA / NCI NIH HHS / United States