Targeting Hypoxic Tumor Microenvironments: Biocompatible and Stable MPC-BA Micelles in Breast Cancer Treatment.

Photodynamic therapy (PDT) is a clinically effective treatment that harnesses the generation of reactive oxygen species (ROS) by photosensitizers upon light activation at specific wavelengths to induce apoptosis in tumor cells. Despite its high precision targeting and minimal systemic toxicity, PDT is constrained by limited light penetration and a reliance on oxygen availability. To surmount these challenges, this study introduced 2-methacryloyloxyethyl- phosphorylcholine (MPC) as a pivotal monomer in the development of nanoscale drug delivery systems. The distinctive phosphatidylcholine structure of MPC confers the material with excellent hydrophilicity, biocompatibility, and prolonged circulation, thereby enhancing the stability of drug carriage and the enrichment efficiency at the tumor site. Building upon these properties, we have synthesized a MPC-butyl acrylate (MPC-BA) amphiphilic block copolymer nanoplatform designed for the concurrent delivery of the photosensitizer chlorin e6 (Ce6) and the chemotherapeutic agent doxorubicin (DOX). Our experimental findings reveal that this nanoplatform facilitates efficient drug release under the acidic conditions of the tumor microenvironment and upon laser stimulation. Furthermore, it exhibits pronounced synergistic antitumor effects in in vitro experiments, underscoring its potential to augment the efficacy of combined PDT and chemotherapy. This nanodrug delivery strategy addresses both the limitations of standalone PDT and also paves the way for a more effective integrated approach to cancer treatment, offering a promising avenue for future therapeutic advancements.