Tumor inflammation-specific self-amplifying fluorescent molecular probes induce an anti-tumor immune response  

作　　者：Shuguang Yang Lijun Hu Hong Xiao Zecong Xiao Xintao Shuai 

机构地区：[1]PCFM Lab of Ministry of Education,School of Materials Science and Engineering,Sun Yat-sen University,Guangzhou 510275,China [2]Nanomedicine Research Center,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China [3]Department of Medical Ultrasound,The Third Affiliated Hospital of Sun Yat-sen University,Guangzhou 510630,China [4]Department of Ultrasound,The Fifth Affiliated Hospital,Sun Yat-sen University,Zhuhai 519000,China

出　　处：《Science China Chemistry》2025年第1期273-287,共15页中国科学(化学英文版)

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。

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 MPO.Meanwhile,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.

关 键 词：fluorescent molecular probes self-amplifying MYELOPEROXIDASE photodynamic therapy 

分 类 号：R730.51[医药卫生—肿瘤] O657.3[医药卫生—临床医学]