CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, University of Chinese Academy of Sciences, Beijing, 100190, China.
Institute for Advanced Interdisciplinary Research, University of Jinan, Jinan, 250022, China.
Angew Chem Int Ed Engl. 2021 Nov 22;60(48):25328-25338. doi: 10.1002/anie.202106750. Epub 2021 Sep 16.
Nanozyme-based catalytic tumor therapy is an emerging therapeutic method with high reactivity in response to tumor microenvironments (TMEs). To overcome the current limitations of deficient catalytic activity of nanozymes, we studied the contributing factors of enzymatic activity based on non-metallic-atom doping and irradiation. Nitrogen doping significantly enhanced the peroxidase activity of Ti-based nanozymes, which was shown experimentally and theoretically. Based on the excellent NIR-adsorption-induced surface plasmon resonance and photothermal effect, the enzymatic activity of TiN nanoparticles (NPs) was further improved under NIR laser irradiation. Hence, an acidic TME-responsive and irradiation-mediated cascade nanocatalyst (TLGp) is presented by using TiN-NP-encapsulated liposomes linked with pH-responsive PEG-modified glucose oxidase (GOx). The integration of pH-responsive GOx-mediated H O self-supply, nitrogen-doping, and irradiation-enhanced enzymatic activity of TiN NPs and mild-photothermal therapy enables an effective tumor inhibition by TLGp with minimal side effects in vivo.
基于纳米酶的催化肿瘤治疗是一种新兴的治疗方法，它在响应肿瘤微环境（TMEs）方面具有高反应性。为了克服纳米酶催化活性不足的当前限制，我们研究了基于非金属原子掺杂和辐照的酶活性贡献因素。氮掺杂显著提高了基于 Ti 的纳米酶的过氧化物酶活性，这在实验和理论上都得到了证实。基于优异的近红外吸收诱导的表面等离子体共振和光热效应，TiN 纳米颗粒（NPs）在近红外激光照射下进一步提高了酶活性。因此，通过使用 TiN-NP 封装的脂质体与 pH 响应的聚乙二醇修饰的葡萄糖氧化酶（GOx）连接，提出了一种酸性 TME 响应和辐照介导的级联纳米催化剂（TLGp）。pH 响应的 GOx 介导的 H2O 自供给、氮掺杂、TiN NPs 的辐照增强酶活性以及温和的光热治疗的整合，使 TLGp 在体内具有最小的副作用，能够有效地抑制肿瘤。
