文献类型：期刊文献

英文题名：Enzyme-Triggered Self-Immobilization of an NIR Prodrug for Tumor-Selective Cancer Vaccination

作者：Li, Yuyao[1];Ren, Hongze[1];Feng, Jiayi[1];Shan, Xiaochuan[2];Zhang, Chaoying[3];Nan, Jin[4];Tang, Zhengqi[1];Ding, Xueqin[1];Yu, Meihua[1];Xie, Hexin[3];Chen, Yu[1,5]

机构：[1]Shanghai Univ, Sch Life Sci, Materdicine Lab, Shanghai 200444, Peoples R China;[2]Nantong Univ, Dept Med Ultrasound, Affiliated Hosp, Nantong 226001, Peoples R China;[3]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Frontiers Sci Ctr Materiobiol & Dynam Chem, State Key Lab Bioreactor Engn,Sch Pharm, Shanghai 200237, Peoples R China;[4]Fudan Univ, Huashan Hosp, Natl Ctr Neurol Disorders, Dept Radiol,State Key Lab Med Neurobiol, Shanghai 200040, Peoples R China;[5]Shanghai Inst Materdicine, Shanghai 200051, Peoples R China

年份：2026

卷号：148

期号：15

起止页码：15655

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20261720579631);WOS:【SCI-EXPANDED(收录号:WOS:001738017100001)】；

基金：The authors gratefully acknowledge the financial support from the National Key Research and Development Projects (Grant No. 2023YFC2306500), the National Natural Science Foundation of China (Grant No. 52572305, 22477024, and 22207035), the Shanghai Science and Technology Program (Grant No. 24520712900), the Fundamental Research Funds for the Central Universities, and the Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism (Shanghai Municipal Education Commission, grant 2021 Sci & Tech 03-28).

语种：英文

外文关键词：Antigens - Cell death - Cell immobilization - Chemical activation - Diseases - Pathology - Tumors - Vaccines

摘要：In situ cancer vaccination, a strategy leveraging tumor antigens released from dying cancer cells to elicit antigen-specific immunity, has emerged as a highly promising modality in cancer immunotherapy. However, prevailing methodologies are constrained by insufficient selectivity for tumor killing, leading to off-target toxicity toward surrounding immune cells and consequently undermining the efficacy of in situ cancer vaccination. Herein, we develop an unprecedented self-immobilizing near-infrared (NIR) prodrug, ALPICD-2, which enables precise and efficacious in situ cancer vaccination through the synergistic integration of targeted ablation of cancer cells and preservation of tumor-infiltrating immune cells (TIICs). Mechanistically, upon activation by alkaline phosphatase enzyme overexpressed on cancer cells, the prodrug ALPICD-2 undergoes a pronounced hydrophilic switch, promoting its selective internalization and covalent self-immobilization into cancer cells with minimal off-target effects, accompanied by the activation of NIR fluorescence that enables real-time monitoring. The tumor-enriched prodrug induces potent cytotoxicity and immunogenic cell death, thereby initiating a cascade of innate and adaptive immune responses. Notably, this covalent immobilizing therapeutics effectively inhibits tumor growth and confers protection against tumor metastasis by enhancing the infiltration of effector CD8+ T cells and natural killer cells within tumor sites while suppressing the immunosuppressive TIICs. This study provides a powerful strategy and precise small-molecular platform for advancing in situ cancer vaccination.