文献类型：期刊文献

英文题名：Enzyme-Activatable Near-Infrared Photosensitizer with High Enrichment in Tumor Cells Based on a Multi-Effect Design

作者：Li, Yuyao[1,2];Zhang, Chaoying[1];Wu, Qingyi[1];Peng, Yan[1];Ding, Yiru[1];Zhang, Zhengwei[3,4];Xu, Xiaoyong[2];Xie, Hexin[1]

机构：[1]East China Univ Sci & Technol, Frontiers Sci Ctr Materiobiol & Dynam Chem, Shanghai Frontier Sci Res Base Optogenet Tech Cell, Sch Pharm,State Key Lab Bioreactor Engn,Shanghai K, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[3]Fudan Univ, Huashan Hosp, Dept Nucl Med, Shanghai 200235, Peoples R China;[4]Fudan Univ, Huashan Hosp, PET Ctr, Shanghai 200235, Peoples R China

年份：2024

卷号：63

期号：7

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20240215365425);WOS:【SCI-EXPANDED(收录号:WOS:001139647100001)】；

基金：Financial supports from the NSFC (22077031 and 22207035), China postdoctoral science foundation (2022M711149), the Fundamental Research Funds for the Central Universities, and Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, grant 2021 Sci & Tech 03-28) are greatly appreciated.

语种：英文

外文关键词：Enzyme-Activatable; Fluorescence Probe; Photosensitizer; Quinone Methide; Tumor

摘要：Enzyme-activatable near-infrared (NIR) fluorescent probes and photosensitizers (PSs) have emerged as promising tools for molecular imaging and photodynamic therapy (PDT). However, in living organisms selective retention or even enrichment of these reagents after enzymatic activation at or near sites of interest remains a challenging task. Herein, we integrate non-covalent and covalent retention approaches to introduce a novel "1-to-3" multi-effect strategy-one enzymatic stimulus leads to three types of effects-for the design of an enzyme-activatable NIR probe or PS. Using this strategy, we have constructed an alkaline phosphatase (ALP)-activatable NIR fluorogenic probe and a NIR PS, which proved to be selectively activated by ALP to switch on NIR fluorescence or photosensitizing ability, respectively. Additionally, these reagents showed significant enrichment (over 2000-fold) in ALP-overexpressed tumor cells compared to the culture medium, accompanied by massive depletion of intracellular thiols, the major antioxidants in cells. The investigation of this ALP-activatable NIR PS in an in vivo PDT model resulted in complete suppression of HeLa tumors and full recovery of all tested mice. Encouragingly, even a single administration of this NIR PS was sufficient to completely suppress tumors in mice, demonstrating the high potential of this strategy in biomedical applications. We report a multi-effect "1-to-3" strategy-one enzymatic stimulus leads to three effects-with the design of an enzyme-activatable, tumor cell-targeting fluorogenic probe and photosensitizer (PS). This PS is selectively activated by alkaline phosphatase, which is overexpressed in tumor cells and causes enrichment of the PS in these cells upon a change in hydrophobicity, resulting in turn-on near-infrared fluorescence and photosensitizing ability.image