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.