Co-delivery systems of paclitaxel prodrug for targeted synergistic therapy of breast cancer

Abstract

This study reported a co-delivery system of paclitaxel (PTX) and doxorubicin (DOX) based on a functionalized poly(ϵ-caprolactone) (FC) conjugated with folate (FA) and PTX prodrug (FA-FC-PTX). PTX was conjugated to pendant carboxyl groups of FC by esterification, and FA was modified to PEG block of FC. The release behaviors of DOX and PTX from the micelles of FA-FC-PTX loaded with DOX (FA-FC-PTX/DOX) were obviously different. DOX was almost completely released in the initial 24 h, while a small amount of PTX was only released for 24 h, and continued to be released for 7 days. The cellular uptake results showed that FA-FC-PTX/DOX could be more effectively internalized by 4T1 cell than the non-folate drug-loaded micelles. In vitro cytotoxicity assays demonstrated that FA-FC-PTX/DOX revealed synergistic effect in inhibiting the proliferation of 4T1 mouse breast cancer cells. Cell apoptosis assays showed that FA-FC-PTX/DOX had the highest apoptosis rate in all drug formulations, indicating that it had high ability to induce cell apoptosis. Furthermore, it was found that FA-FC-PTX/DOX exhibited better inhibition effect on 4T1 tumor growth compared with free PTX/DOX combination or non-folate drug-loaded micelles and there was no obvious side effect on the 4T1 tumor-bearing mice. Thus, this work provides a promising drug co-delivery system for targeted therapy of breast cancer.