Nanocatalytic Tumor Therapy by Biomimetic Dual Inorganic Nanozyme-Catalyzed Cascade Reaction
Nanocatalytic Tumor Therapy by Biomimetic Dual Inorganic Nanozyme-Catalyzed Cascade Reaction
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DOI：
10.1002/advs.201801733
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发表时间：
2019-02-06
期刊：
影响因子：
15.1
通讯作者：
Shi, Jianlin
中科院分区：
文献类型：
--
作者：
Gao, Shanshan;Lin, Han;Shi, Jianlin
基于无毒但具有催化活性的无机纳米颗粒（NPs）用于肿瘤内产生高毒性活性氧的新兴纳米催化肿瘤疗法激发了科学界的极大研究兴趣。具有天然酶模拟催化活性的纳米酶在生物医学中得到了广泛的研究，主要用于生物分子检测，但在特异性纳米催化肿瘤治疗方面的研究却少得多。本研究报道了一种基于纳米酶的高效仿生双无机纳米平台的构建，其基于超小Au和Fe 3 O 4纳米颗粒与树枝状介孔二氧化硅纳米颗粒共载，引发肿瘤微环境响应性纳米催化肿瘤治疗的级联催化反应。Au NPs作为独特的葡萄糖氧化酶模拟纳米酶特异性地催化β-D-葡萄糖氧化成葡萄糖酸和H2 O2，而所产生的H2 O2随后被过氧化物酶模拟Fe 3 O 4 NPs催化以释放高毒性的羟基自由基，用于通过典型的基于Fenton的催化反应诱导肿瘤细胞死亡。广泛的体外和体内评价表明，基于这些生物相容性复合纳米催化剂的高纳米催化剂治疗效果与理想的肿瘤抑制率（69.08%）。因此，本研究为合理设计具有多种酶活性的无机纳米酶，实现高效、安全的肿瘤纳米催化治疗奠定了基础。
Emerging nanocatalytic tumor therapies based on nontoxic but catalytically active inorganic nanoparticles (NPs) for intratumoral production of high-toxic reactive oxygen species have inspired great research interest in the scientific community. Nanozymes exhibiting natural enzyme-mimicking catalytic activities have been extensively explored in biomedicine, mostly in biomolecular detection, yet much fewer researches are available on specific nanocatalytic tumor therapy. This study reports on the construction of an efficient biomimetic dual inorganic nanozyme-based nanoplatform, which triggers cascade catalytic reactions for tumor microenvironment responsive nanocatalytic tumor therapy based on ultrasmall Au and Fe3O4 NPs coloaded dendritic mesoporous silica NPs. Au NPs as the unique glucose oxidase-mimic nanozyme specifically catalyze beta-D-glucose oxidation into gluconic acid and H2O2, while the as produced H2O2 is subsequently catalyzed by the peroxidase-mimic Fe3O4 NPs to liberate high-toxic hydroxyl radicals for inducing tumor-cell death by the typical Fenton-based catalytic reaction. Extensive in vitro and in vivo evaluations have demonstrated high nanocatalytic-therapeutic efficacy with a desirable tumor-suppression rate (69.08%) based on these biocompatible composite nanocatalysts. Therefore, this work paves a way for nanocatalytic tumor therapy by rationally designing inorganic nanozymes with multienzymatic activities for achieving high therapeutic efficacy and excellent biosafety simultaneously.