Photodynamic therapy (PDT) has become an attractive tumor treatment modality because of its noninvasive feature and low side effects. However, extreme hypoxia inside solid tumors severely impedes PDT therapeutic outcome. To overcome this obstacle, various strategies have been developed recently. Among them, in situ oxygen generation, which relies on the decomposition of tumor endogenous H₂O₂, and oxygen delivery tactic using high oxygen loading capacity of hemoglobin or perfluorocarbons, have been widely studied. The in situ oxygen generation strategy has high specificity to tumors, but its oxygen-generating efficiency is limited by the intrinsically low tumor H₂O₂ level. In contrast, the oxygen delivery approach holds advantage of high oxygen loading efficiency, nevertheless lacks tumor specificity. In this work, we prepared a nanoemulsion system containing H₂O₂-responsive catalase, highly efficient oxygen carrier perfluoropolyether (PFPE), and a near-infrared (NIR) light activatable photosensitizer IR780, to combine the high tumor specificity of the in situ oxygen generation strategy and the high efficiency of the oxygen delivery strategy. This concisely prepared nanoplatform exhibited enhanced and H₂O₂-controllable production of singlet oxygen under light excitation, satisfactory cytocompatibility, and ability to kill cancer cells under NIR light excitation. This highlights the potential of this novel nanoplatform for highly efficient and selective NIR light mediated PDT against hypoxic tumors. This research provides new insight into the design of intelligent nanoplatform for relieving tumor hypoxia and enhancing the oxygen-dependent PDT effects in hypoxic tumors.

中文翻译：

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使用相转化组合法开发用于光动力治疗缺氧肿瘤的过氧化氢响应和携氧纳米乳

光动力疗法（PDT）由于其无创性和低副作用已成为一种有吸引力的肿瘤治疗方式。然而，实体瘤内的极度缺氧严重阻碍了 PDT 的治疗效果。为了克服这个障碍，最近开发了各种策略。他们之中，原位依赖于肿瘤内源性H ₂ O ₂分解的氧气产生，以及利用血红蛋白或全氟化碳的高载氧能力的氧气输送策略已被广泛研究。这原位制氧策略对肿瘤具有较高的特异性，但其制氧效率受限于肿瘤固有的低H ₂ O ₂水平。相比之下，氧气输送方法具有高氧负荷效率的优势，但缺乏肿瘤特异性。在这项工作中，我们制备了包含 H ₂ O ₂响应性过氧化氢酶、高效氧载体全氟聚醚 (PFP​​E) 和近红外 (NIR) 光激活光敏剂 IR780 的纳米乳液体系，以结合其高肿瘤特异性。原位氧气产生策略和氧气输送策略的高效率。这种简洁制备的纳米平台在光激发下表现出增强的和 H ₂ O ₂可控的单线态氧产生、令人满意的细胞相容性以及在 NIR 光激发下杀死癌细胞的能力。这凸显了这种新型纳米平台在针对缺氧肿瘤的高效和选择性 NIR 光介导的 PDT 方面的潜力。该研究为智能纳米平台的设计提供了新的见解，用于缓解肿瘤缺氧并增强缺氧肿瘤中的氧依赖性PDT效应。