文献类型：期刊文献

英文题名：A cascade-responsive nanoplatform for cyclooxygenase-2 inhibition and inflammation regulation to enhance photoimmunotherapy

作者：Zhang, Jingyan[1];Zheng, Jiahao[1];Wang, Yuan[1];Tian, Jia[1,2];Zhang, Weian[1,2]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab Funct Mat Chem, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Sch Mat Sci & Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2026

卷号：217

起止页码：680

外文期刊名：ACTA BIOMATERIALIA

收录：;EI(收录号：20262120769749);WOS:【SCI-EXPANDED(收录号:WOS:001793870800001)】；

基金：This work was financially supported by the National Natural Science Foundation of China (No. 52333014 and 22575086) and the Science and Technology Commission of Shanghai Municipality (No. 24520713200 and BJKJ2024054) .

语种：英文

外文关键词：Photoimmunotherapy; Inflammation; COX-2; Indomethacin

摘要：Photodynamic immunotherapy (PIT) has emerged as a promising cancer treatment by photo-activating host immune system to eliminate tumor. However, excessive oxidative stress generated during PIT often induces uncontrolled inflammatory responses and activates immunosuppressive pathways to determine the efficacy of PIT. Herein, we developed a cascade responsive nanoplatform (FBC@PTI) to reduce the inflammation level by co-assembly of an indomethacin-based amphiphilic block copolymer and photosensitizer tetrafluorophenyl bacterial chlorophyll (FBC). Under acidic TME conditions, FBC@PTI underwent surface charge reversal to facilitate tumor penetration and cell internalization. Upon 750 nm light irradiation, FBC could not only generate robust reactive oxygen species (ROS) to induce immunogenic cell death (ICD), but also trigger the disassociation of FBC@PTI to release indomethacin, and inhibit cyclooxygenase-2 (COX-2) to reduce inflammatory level. In vivo experiments demonstrated that the released indomethacin can effectively suppress the expression level of COX-2 (61.1%) and PGE2 (66.5%), and then reduce the inflammatory factor level of TNF-alpha (25.8%) and IL-6 (74.0%) from macrophages. As a result, immune activity could further elevate to enhance CD4* and CD8* T cell infiltration and reduce Treg accumulation under controllable inflammatory level. This strategy of regulating inflammation in PIT would offer a potential path for improving the efficacy of PIT. Statement of significance: We developed a cascade responsive nanoplatform (FBC@PTI) that integrates photoimmunotherapy with programmable inflammation modulation. Enabled by pH-triggered charge reversal and light-induced ROS generation, this system enhances tumor-targeted delivery, induces immunogenic cell death, and simultaneously releases indomethacin to inhibit COX-2-mediated inflammatory signaling. By coordinating immune activation with precise inflammation regulation, this strategy offers a promising approach to improve the therapeutic efficacy of photoimmunotherapy.