mPEG-b-PCL/TPGS mixed micelles for delivery of resveratrol in overcoming resistant breast cancer.
OBJECTIVE
Drug resistance remains a major challenge for effective breast cancer chemotherapy. Resveratrol (Res) is a promising candidate for overcoming cancer chemoresistance, but it has low bioavailability due to poor absorption, and ready metabolism limits its application. This study aims to develop a Res-loaded mixed micelle system to be effective on drug resistance of breast cancer cells.


METHODS
A mixed micelle system made of methoxy poly (ethylene glycol)-b-polycaprolactone (mPEG-PCL) and d-α-Tocopherol polyethylene glycol succinate was prepared and Res was encapsulated to form Res-loaded mixed micelles. Furthermore, the antitumor activity against doxorubicin (Dox)-resistant breast cancer MCF-7/ADR cells was studied and the possible mechanism was elucidated.


RESULTS
The mixed micellar formulation increased drug uptake efficiency of Res by Dox-resistant breast cancer MCF-7/ADR cells, and induced higher rates of apoptotic cell death, as assessed by the accumulation of Sub G1 phases of cell cycle, nucleus staining and Annexin-FITC/propidium iodide assay. Moreover, Res-loaded mixed micelles also markedly enhanced Dox-induced cytotoxicity in MCF-7/ADR cells and increased the cellular accumulation of Dox by downregulating the expression of P-glycoprotein (P-gp) and inhibiting the activity thereof.


CONCLUSIONS
The cumulative evidence indicates that Res-loaded mixed micelles hold significant promise for the treatment of drug-resistant breast cancer.
University of Macau, Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine , Macau, 999078 , China.
Shengpeng
S
Wang
Ruie
R
Chen
Joe
J
Morott
Michael A
MA
Repka
Yitao
Y
Wang
Meiwan
M
Chen
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000096:biosynthesis; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers; D004361:Drug Tolerance; D006801:Humans; D008823:Micelles; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage* / Q000494:pharmacology; D014810:Vitamin E / Q000031:analogs & derivatives* / Q000737:chemistry
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004337:Drug Carriers; D008823:Micelles; D011091:Polyesters; D013267:Stilbenes; C439611:methoxy poly(ethylene glycol-co-epsilon-caprolactone); D014810:Vitamin E; D011092:Polyethylene Glycols; C014225:tocophersolan; D000077185:Resveratrol
Tocopherol polyethylene glycol succinate; breast cancer resistance; mPEG-b-PCL; mixed micelles; resveratrol