Tumor inflammation-specific self-amplifying fluorescent molecular probes induce an anti-tumor immune response
作者机构：PCFM Lab of Ministry of Education School of Materials Science and Engineering Sun Yat-sen University Department of Ultrasound The Fifth Affiliated Hospital Sun Yat-sen University Department of Medical Ultrasound The Third Affiliated Hospital of Sun Yat-sen University Nanomedicine Research Center The Third Affiliated Hospital of Sun Yat-sen University
出 版 物：《Science China Chemistry》 (中国科学:化学(英文版))
年 卷 期：2025年第68卷第1期
页 面：273-287页
核心收录：
学科分类：081704[工学-应用化学] 1002[医学-临床医学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070302[理学-分析化学] 100214[医学-肿瘤学] 0703[理学-化学] 10[医学]
基 金：supported by the Key Areas Research and Development Program of Guangzhou (202007020006) the National Natural Science Foundation of China (51933011, 31971296, 82102194,82302360) the Science and Technology Projects of Guangzhou(2023A03J0215) the Guangdong Basic Research Center of Excellence for Functional Molecular Engineering
主 题：fluorescent molecular probes self-amplifying myeloperoxidase photodynamic therapy
摘 要：Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy. Nonetheless, the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes. Herein, we reported a self-amplifying fluorescent molecular probe, Bis-HTPICG, for photodynamic therapy(PDT) and subsequent PDT-induced immunoreaction. The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO), a crucial enzyme secreted by neutrophils at inflammation sites. Upon exposure to laser irradiation, Bis-HTP-ICG showed a high PDT efficacy, inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion. The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis, instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG, neutrophils and ***, PDT efficiently incites immunogenic cell death(ICD) in tumor cells, initiating an anti-tumor immune response including dendritic cells(DCs) maturation, T cell proliferation and reprogramming of tumor-associated neutrophils(TANs). This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.
同方期刊数据库