pH-Responsive Amphiphilic Triblock Fluoropolymers as Assemble Oxygen Nanoshuttles for Enhancing PDT against Hypoxic Tumor

Photodynamic therapy (PDT) is a cancer treatment strategy that utilizes photosensitizers to convert oxygen within tumors into reactive singlet oxygen ( 1 O 2 ) to lyse tumor cells. Nevertheless, pre-existing tumor hypoxia and oxygen consumption during PDT can lead to an insufficient oxygen supply, potentially reducing the photodynamic efficacy. In response to this issue, we have devised a pH-responsive amphiphilic triblock fluorinated polymer (PDP) using copper-mediated RDRP. This polymer, composed of poly(ethylene glycol) methyl ether acrylate, 2-(diethylamino)ethyl methacrylate, and (perfluorooctyl)ethyl acrylate, self-assembles in an aqueous environment. Oxygen, chlorine e6 (Ce6), and doxorubicin (DOX) can be codelivered efficiently by PDP. The incorporation of perfluorocarbon into the formulation enhances the oxygen-carrying capacity of PDP, consequently extending the lifetime of 1 O 2 . This increased lifetime, in turn, amplifies the PDT effect and escalates the cellular cytotoxicity. Compared with PDT alone, PDP@Ce6-DOX-O 2 NPs demonstrated significant inhibition of tumor growth. This study proposes a novel strategy for enhancing the efficacy of PDT.

光动力疗法（PDT）是一种癌症治疗策略，利用光敏剂将肿瘤内的氧转化为活性单线态氧（ 1 O 2 ）来裂解肿瘤细胞。然而，PDT 期间预先存在的肿瘤缺氧和耗氧量可能会导致供氧不足，从而可能降低光动力功效。针对这个问题，我们使用铜介导的 RDRP 设计了一种 pH 响应型两亲性三嵌段氟化聚合物 (PDP)。这种聚合物由聚(乙二醇)甲醚丙烯酸酯、甲基丙烯酸2-(二乙氨基)乙酯和丙烯酸(全氟辛基)乙酯组成，在水性环境中自组装。 PDP 可以有效地共同传递氧气、氯 e6 (Ce6) 和阿霉素 (DOX)。配方中加入全氟化碳可增强 PDP 的携氧能力，从而延长 1 O 2 的使用寿命。寿命的延长反过来又放大了 PDT 效果并增强了细胞的细胞毒性。与单独的PDT相比，PDP@Ce6-DOX-O 2 NPs表现出显着的肿瘤生长抑制作用。这项研究提出了一种增强 PDT 疗效的新策略。