Beyond the Roles in Biomimetic Chemistry: An Insight into the Intrinsic Catalytic Activity of an Enzyme for Tumor-Selective Phototheranostics.
Beyond the Roles in Biomimetic Chemistry: An Insight into the Intrinsic Catalytic Activity of an Enzyme for Tumor-Selective Phototheranostics.
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超越仿生化学的作用：深入了解肿瘤选择性光治疗酶的内在催化活性
DOI：
10.1021/acsnano.8b05797
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发表时间：
2018
期刊：
影响因子：
17.1
通讯作者：
Zhang Bingbo
中科院分区：
文献类型：
--
作者：
Yang Weitao;Shi Xiudong;Shi Yuxin;Yao Defan;Chen Shizhen;Zhou Xin;Zhang Bingbo
蛋白质辅助仿生合成因其具有绿色化学、工艺简单、易于多学科集成等特点，成为近年来纳米纤维领域的一个新兴分支。因此，许多蛋白质已被用于各种纳米结构的仿生合成。尽管人们对新蛋白质的探索和对它们在仿生化学中作用的研究不断增加，但蛋白质最基本的内在性质却被忽视了。本文报道了一种常用的酶（辣根过氧化物酶，HRP）在完成超小钆（Gd）纳米点的仿生合成并装载其底物2，2 ′-连氮双（3-乙基苯并噻唑啉-6-磺酸铵盐）（ABTS）（记为Gd@HRPABTS）后，证明酶活性保留的可能性。它被发现thatca。酶活保留率为70%。通过光谱分析研究了化学处理对蛋白质结构的影响。利用高度保留的催化活性，Gd@ HRPABTS在肿瘤内存在固有H2 O2的情况下，对过氧化物酶底物ABTS产生强催化氧化作用，从而实现肿瘤选择性催化光声（PA）成像和光热治疗（PTT）。此外，Gd@ HRPABTS的MR部分为PTT提供了指导，并进一步说明Gd@ HRPABTS可从体内清除。初步毒性研究表明，使用这些药物未观察到不良反应。这项研究表明，除了在仿生化学中的众所周知的作用之外，HRP还可以保留其用于肿瘤催化治疗诊断的酶活性。
Protein-assisted biomimetic synthesis has been an emerging offshoot of nanofabrication in recent years owing to its features of green chemistry, facile process, and ease of multi-integration. As a result, many proteins have been used for biomimetic synthesis of varying kinds of nanostructures. Although the efforts on exploring new proteins and investigating their roles in biomimetic chemistry are increasing, the most essential intrinsic properties of proteins are largely neglected. Herein we report a frequently used enzyme (horseradish peroxidase, HRP) to demonstrate the possibility of enzymatic activity retaining after accomplishing the roles in biomimetic synthesis of ultrasmall gadolinium (Gd) nanodots and stowing its substrate 2,2′-Azinobis (3-ethylbenzothiazoline-6-sulfonic acid ammonium salt) (ABTS), denoted as Gd@HRPABTS. It was found thatca. 70% of the enzymatic activity of HRP was preserved. The associated changes of protein structure with chemical treatments were studied by spectroscopic analysis. Leveraging on the highly retained catalytic activity, Gd@HRPABTSexerts strong catalytic oxidation of peroxidase substrate ABTS into photoactive counterparts in the presence of intrinsic H2O2inside the tumor, therefore enabling tumor-selective catalytic photoacoustic (PA) imaging and photothermal therapy (PTT). In addition, the MR moiety of Gd@HRPABTSprovides guidance for PTT and further diagrams that Gd@HRPABTSis clearable from the bodyviakidneys. Preliminary toxicity studies show no observed adverse effects by administration of them. This study demonstrates beyond the well-known roles in biomimetic chemistry that HRP can also preserve its enzymatic activity for tumor catalytic theranostics.