Tumor hypoxia is a typical characteristic of tumor microenvironment (TME), which seriously compromises the therapeutic effect of photodynamic therapy (PDT). The development of nanozymes with oxygen-generation ability is a promising strategy to overcome the oxygen-dependent of PDT but remained a great challenge. Herein, a dual-nanozymes based cascade reactor HAMF is proposed to alleviate tumor hypoxia for enhanced PDT. The hollow mesoporous silica nanoparticles (HMSNs) are constructed as an excellent nanocarrier to load ultra-small gold nanoparticles (Au NPs) and manganese dioxide (MnO₂) shell via in situ reduction method, and further coordination with an efficient photosensitizer 4-DCF-MPYM (4-FM), a thermally activated delayed fluorescence (TADF) fluorescein derivative. With the response to TME, MnO₂ can catalyze endogenous H₂O₂ into O₂ and subsequently accelerating glucose oxidation by Au NPs to produce additional H₂O₂, which is reversely used as the substrate for MnO₂-catalyzed reaction, thereby constantly producing singlet oxygen (¹O₂) for enhanced PDT upon light irradiation. This work proposed a cascade reactor based on dual-nanozyme to relieve tumor hypoxia for effective tumor suppression, which may enrich the application of multi-nanozymes in biomedicine.

中文翻译：

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双纳米酶催化级联反应器用于增强光动力肿瘤治疗肿瘤缺氧

肿瘤缺氧是肿瘤微环境（TME）的典型特征，严重影响了光动力疗法（PDT）的治疗效果。开发具有产氧能力的纳米酶是克服 PDT 氧依赖的一种很有前途的策略，但仍然是一个巨大的挑战。在此，提出了一种基于双纳米酶的级联反应器 HAMF 来缓解肿瘤缺氧以增强 PDT。中空介孔二氧化硅纳米粒子（HMSNs）被构建为一种优秀的纳米载体，通过原位还原法负载超小金纳米粒子（Au NPs）和二氧化锰（MnO ₂）壳，并进一步与高效光敏剂4-DCF-配合MPYM (4-FM)，一种热激活延迟荧光 (TADF) 荧光素衍生物。随着对 TME 的反应，MnO₂可以将内源性 H ₂ O ₂催化为 O ₂并随后通过 Au NPs 加速葡萄糖氧化以产生额外的 H ₂ O ₂，其反向用作 MnO ₂催化反应的底物，从而不断产生单线态氧（¹ O ₂ ) 用于增强光照射后的 PDT。该工作提出了一种基于双纳米酶的级联反应器，以缓解肿瘤缺氧，有效抑制肿瘤，丰富了多纳米酶在生物医学中的应用。