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.

光动力疗法（PDT）是一种临床上有效的治疗方法，利用光敏剂在特定波长的光激活后产生活性氧（ROS）来诱导肿瘤细胞凋亡。尽管 PDT 具有高精度靶向性和最小的全身毒性，但它仍受到有限的光穿透和对氧气可用性的依赖的限制。为了克服这些挑战，本研究引入了 2-甲基丙烯酰氧基乙基磷酰胆碱 (MPC) 作为纳米级药物输送系统开发中的关键单体。 MPC独特的磷脂酰胆碱结构赋予材料优异的亲水性、生物相容性和延长的循环能力，从而增强药物运载的稳定性和在肿瘤部位的富集效率。基于这些特性，我们合成了一种 MPC-丙烯酸丁酯 (MPC-BA) 两亲性嵌段共聚物纳米平台，设计用于同时递送光敏剂二氢卟酚 e6 (Ce6) 和化疗剂阿霉素 (DOX)。我们的实验结果表明，该纳米平台有助于在肿瘤微环境的酸性条件下和激光刺激下有效释放药物。此外，它在体外实验中表现出明显的协同抗肿瘤作用，强调了其增强 PDT 和化疗联合疗效的潜力。这种纳米药物递送策略既解决了独立 PDT 的局限性，也为更有效的癌症治疗综合方法铺平了道路，为未来的治疗进步提供了一条有希望的途径。