Photodynamic therapy (PDT) is a well-known method for cancer therapy in the clinic. However, the inherent hypoxia microenvironment of solid tumors enormously restricts the PDT efficiency. Herein, catalase nanocrystals (CatCry) are introduced as in situ oxygen (O₂)-generating system to relieve tumor hypoxia and enhance PDT efficiency for solid tumors. After loading with photosensitizer methylene blue (MB), a PDT drug platform (CatCry-MB) emerges, allowing for significant increasing PDT efficiency instigated by three factors. First, the high stability and recyclable catalytic activity of CatCry enable a long-term endogenous H₂O₂ decomposition for continuous O₂ supply for sustained relief of tumor hypoxia. Second, both the produced O₂ and loaded MB are confined within CatCry nanoporous structure, shortening the diffusion distance between O₂ and MB to maximize the production of singlet oxygen (¹O₂). Third, the MB molecules are uniformly dispersed within CatCry lattice, avoiding MB aggregation and causing more MB molecules be activated to produce more ¹O₂. With the three complementary mechanisms, tumor hypoxia is eradicated and the resulted enhancement in PDT efficiency is demonstrated in vitro and in vivo. The proposed approach opens up a new venue for the development of other O₂-dependent tumor treatments, such as chemotherapy, radiotherapy, and immunotherapy.

中文翻译：

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载有亚甲蓝的过氧化氢酶纳米晶体作为自供氧的成像引导平台，用于缺氧肿瘤的光动力治疗

光动力疗法（PDT）是临床上众所周知的癌症治疗方法。然而，实体瘤固有的缺氧微环境极大地限制了 PDT 的效率。在此，过氧化氢酶纳米晶体 (CatCry) 被引入作为原位氧 (O ₂ ) 生成系统，以缓解肿瘤缺氧并提高实体瘤的 PDT 效率。加载光敏剂亚甲蓝 (MB) 后，出现了 PDT 药物平台 (CatCry-MB)，允许通过三个因素显着提高 PDT 效率。首先，CatCry 的高稳定性和可回收催化活性能够实现长期内源性 H ₂ O ₂分解，从而持续供应O ₂以持续缓解肿瘤缺氧。其次，产生的O₂和负载的 MB 被限制在 CatCry 纳米多孔结构内，缩短了 O ₂和 MB之间的扩散距离，以最大限度地产生单线态氧 ( ¹ O ₂ )。第三，MB分子均匀地分散在CatCry晶格内，避免MB聚集并导致更多的MB分子被激活以产生更多的¹ O ₂。通过三种互补机制，消除了肿瘤缺氧，并在体外和体内证明了 PDT 效率的提高。所提出的方法为开发其他 O ₂依赖性肿瘤治疗（如化疗、放疗和免疫治疗）开辟了新的途径。