A Mesoporous Nanoenzyme Derived from Metal-Organic Frameworks with Endogenous Oxygen Generation to Alleviate Tumor Hypoxia for Significantly Enhanced Photodynamic Therapy
A Mesoporous Nanoenzyme Derived from Metal-Organic Frameworks with Endogenous Oxygen Generation to Alleviate Tumor Hypoxia for Significantly Enhanced Photodynamic Therapy
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一种源自金属有机框架的介孔纳米酶，具有内源性氧气生成能力，可缓解肿瘤缺氧，从而显着增强光动力治疗
DOI：
10.1002/adma.201901893
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发表时间：
2019-07-01
影响因子：
29.4
通讯作者：
Zhao, Yanli
中科院分区：
文献类型：
--
作者：
Wang, Dongdong;Wu, Huihui;Zhao, Yanli
肿瘤缺氧影响光动力疗法(PDT)的疗效，因为局部氧浓度在细胞毒性单线态氧(O-1(2))的产生中起重要作用。本文介绍了一种由金属有机骨架(MOF)衍生的多功能介孔纳米酶(NE)，用于在生物成像引导下原位产生内源性O-2以增强PDT的效率。首先在锰基金属氧化物纤维表面包覆一层介孔二氧化硅，然后在常压下进行简单的热处理过程，从而构建了介孔纳米管。在去除介孔二氧化硅壳层并用聚多巴胺和聚乙二醇改性以提高生物相容性后，得到的介孔NE负载了PDT中常用的光敏剂四氯乙烯(Ce6)，具有很高的负载量。通过催化量NE和内源性过氧化氢之间的催化反应产生O-2，缓解了缺氧的肿瘤微环境。因此，负载Ce6的NE作为H_2O_2激活的氧供体，可以增加局部的O-2浓度，从而在体内外显著增强PDT的抗肿瘤效果。此外，NE还显示了其体内跟踪的T-2加权磁共振成像能力。这项工作提出了一个有趣的生物医学用途的MOF衍生的介孔去甲肾上腺素作为一种多功能的治疗药物在癌症治疗。
Tumor hypoxia compromises the therapeutic efficiency of photodynamic therapy (PDT) as the local oxygen concentration plays an important role in the generation of cytotoxic singlet oxygen (O-1(2)). Herein, a versatile mesoporous nanoenzyme (NE) derived from metal-organic frameworks (MOFs) is presented for in situ generation of endogenous O-2 to enhance the PDT efficacy under bioimaging guidance. The mesoporous NE is constructed by first coating a manganese-based MOFs with mesoporous silica, followed by a facile annealing process under the ambient atmosphere. After removing the mesoporous silica shell and post-modifying with polydopamine and poly(ethylene glycol) for improving the biocompatibility, the obtained mesoporous NE is loaded with chlorin e6 (Ce6), a commonly used photosensitizer in PDT, with a high loading capacity. Upon the O-2 generation through the catalytic reaction between the catalytic amount NE and the endogenous H2O2, the hypoxic tumor microenvironment is relieved. Thus, Ce6-loaded NE serves as a H2O2-activated oxygen supplier to increase the local O-2 concentration for significantly enhanced antitumor PDT efficacy in vitro and in vivo. In addition, the NE also shows T-2-weighted magnetic resonance imaging ability for its in vivo tracking. This work presents an interesting biomedical use of MOF-derived mesoporous NE as a multifunctional theranostic agent in cancer therapy.