Chen Miaomiao, Song Jitao, Zhu Jialong, Hong Gaobo, An Jing, Feng Erting, Peng Xiaojun, Song Fengling
State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. China.
Institute of Molecular Sciences and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao, 266237, P. R. China.
Adv Healthc Mater. 2021 Nov;10(21):e2101049. doi: 10.1002/adhm.202101049. Epub 2021 Sep 8.
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 (MnO ) 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, MnO can catalyze endogenous H O into O and subsequently accelerating glucose oxidation by Au NPs to produce additional H O , which is reversely used as the substrate for MnO -catalyzed reaction, thereby constantly producing singlet oxygen ( O ) 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.
肿瘤缺氧是肿瘤微环境（TME）的典型特征，严重影响光动力疗法（PDT）的治疗效果。开发具有产氧能力的纳米酶是克服PDT对氧依赖性的一种有前景的策略，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，以缓解肿瘤缺氧，增强PDT效果。通过原位还原法构建中空介孔二氧化硅纳米颗粒（HMSNs）作为优良的纳米载体，负载超小金纳米颗粒（Au NPs）和二氧化锰（MnO₂）壳层，并进一步与高效光敏剂4-DCF-MPYM（4-FM）（一种热激活延迟荧光（TADF）荧光素衍生物）配位。随着对TME的响应，MnO₂可以将内源性H₂O₂催化生成O₂，随后加速Au NPs催化葡萄糖氧化以产生额外的H₂O₂，而H₂O₂又反过来用作MnO₂催化反应的底物，从而在光照下不断产生单线态氧（¹O₂）以增强PDT效果。这项工作提出了一种基于双纳米酶的级联反应器来缓解肿瘤缺氧，实现有效的肿瘤抑制，这可能会丰富多纳米酶在生物医学中的应用。
