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具有激光激活 O 供应和光热增强功能的三重级联纳米催化剂,用于有效治疗缺氧肿瘤的催化治疗。

Triple cascade nanocatalyst with laser-activatable O supply and photothermal enhancement for effective catalytic therapy against hypoxic tumor.

机构信息

State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin, 300071, China.

State Key Laboratory of Medicinal Chemical Biology and Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin, 300071, China; College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, 201620, China.

出版信息

Biomaterials. 2022 Jan;280:121308. doi: 10.1016/j.biomaterials.2021.121308. Epub 2021 Dec 8.

DOI:10.1016/j.biomaterials.2021.121308
PMID:34896860
Abstract

Nanozymes have been combined with glucose oxidase (GOx) for dual-enzyme cascade catalytic therapy. However, their catalysis efficiency is restricted because of the hypoxia tumor microenvironment (TME). Although many methods are developed for O supply, the O leakage and consumption of HO compromised their practical application. Herein, a biocompatible carbon nitride (CN)/nanozyme/GOx triple cascade nanocatalyst was designed with laser-activatable O self-supply via water splitting to relieve tumor hypoxia and thus improve the catalysis efficiency. To this end, polydopamine (PDA) nanosphere was prepared and attached with CN nanosheet to improve water splitting efficiency and realize photothermal-enhanced catalysis, simultaneously. The PDA@CN composite was then coated with MIL-100 (Fe), where GOx was loaded, to form CN/MIL-100/GOx triple cascade nanocatalyst. The triple cascade catalysis was realized with laser-activatable O supply from PDA@CN, HO generation with GOx, and •OH production from peroxidase-like MIL-100 (Fe) for tumor therapy. Upon 808 nm irradiation, PDA, as a photothermal agent, realized photothermal therapy and enhanced the catalytic therapy. Thus, the synergy of laser-activatable O supply and photothermal enhancement in our triple cascade nanocatalyst improved the performance of catalytic therapy without drug resistance and toxicity to normal tissues.

摘要

纳米酶已与葡萄糖氧化酶(GOx)结合,用于双酶级联催化治疗。然而,由于缺氧肿瘤微环境(TME),它们的催化效率受到限制。尽管已经开发了许多供氧方法,但 O 泄漏和 HO 的消耗使其实际应用受到限制。在此,设计了一种具有激光激活的 O 自供应功能的生物相容性碳氮化物(CN)/纳米酶/GOx 三重级联纳米催化剂,通过水分解来缓解肿瘤缺氧,从而提高催化效率。为此,制备了聚多巴胺(PDA)纳米球,并将其附着到 CN 纳米片上,以提高水分解效率并实现光热增强催化,同时。然后将 PDA@CN 复合材料包覆在 MIL-100(Fe)上,负载 GOx,形成 CN/MIL-100/GOx 三重级联纳米催化剂。三重级联催化通过 PDA@CN 的激光激活 O 供应、GOx 产生 HO 和过氧化物酶样 MIL-100(Fe)产生 •OH 来实现,用于肿瘤治疗。在 808nm 照射下,作为光热剂的 PDA 实现了光热治疗,并增强了催化治疗。因此,我们的三重级联纳米催化剂中激光激活 O 供应和光热增强的协同作用提高了催化治疗的性能,而不会产生耐药性和对正常组织的毒性。

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