mPEG-g-CS-Modified PLGA Nanoparticle Carrier for the Codelivery of Paclitaxel and Epirubicin for Breast Cancer Synergistic Therapy.

The aim of this study was to investigate a novel double-layer core-shell structure nanoparticle (NP) delivery system, comprising a nanoscale self-assembly mPEG-g-CS envelope coating on a nuclear PLGA NPs. We then constructed the core-shell NPs for paclitaxel (PTX) loading in the outer envelope to target tumor neovasculature and epirubicin (EPI) loading in the core to antitumor cells. We characterized the NPs for physical/chemical properties, controlled drug release kinetics, and finally evaluated in vitro and in vivo antitumor activities. It could be seen that these three blank NPs (core-shell NPs, PLGA NPs, and mPEG-g-CS NPs) had no significant influence on the cell viability of human breast adenocarcinoma cell line (MCF-7) and human umbilical vein endothelial cells (HUVEC) in a NPs concentration range of 0.5-1000 μg/mL for 24 and 48 h, thus it can be inferred that the NPs constructed by mPEG-g-CS and PLGA polymers have good biocompatibility for further application. The confocal images and flow cytometry results showed that the core-shell NPs were efficiently internalized by these cells. After intravenous injection to nude mice bearing MCF-7 breast tumor, core-shell NPs achieved enhanced antitumor and antiangiogenic effects, prolonged retention, increased distribution, and significantly reduced microvessel density (MVD) in tumor tissues compared to both PLGA NPs and mPEG-g-CS NPs. In conclusion, this novel NPs system represent a new way of combining traditional combination chemotherapy and antiangiogenesis therapy for controlled drug delivery applications, and appeared to be a promising combination therapy to treat breast cancer.