文献类型：期刊文献

英文题名：Pretargeted Multimodal Tumor Imaging by Enzymatic Self-Immobilization Labeling and Bioorthogonal Reaction

作者：Miao, Yinxing[1];Wang, Yuqi[1];Chen, Yefeng[2];Huang, Zheng[1];Lu, Chunmei[1];Liu, Yili[1];Chen, Fangfang[2];Wen, Xidan[1];Zhang, Junya[1];Zhu, Shiliang[3];Zhao, Pengke[1];Chen, Yunhan[1];Tian, Tian[1];Zhang, Yan[1];Xie, Hexin[2];Lin, Jianguo[3];Ye, Deju[1]

机构：[1]Nanjing Univ, Chem & Biomed Innovat Ctr ChemBIC, Sch Chem & Chem Engn, State Key Lab Analyt Chem Life Sci, Nanjing 210023, Peoples R China;[2]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[3]Jiangsu Inst Nucl Med, NHC Key Lab Nucl Med, Jiangsu Key Lab Mol Nucl Med, Wuxi 214063, Peoples R China

年份：2025

卷号：147

期号：3

起止页码：2809

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20250317706291);WOS:【SCI-EXPANDED(收录号:WOS:001395878800001)】；

基金：We thank Prof. Peng Zheng from School of Chemistry and Chemical Engineering, Nanjing University to share us with GFP proteins. We acknowledge the financial support from the National Natural Science Foundation of China (22137003, 22225703, 22274074, and 22077031), Joint Funds for the innovation of Science and Technology in Fujian Province (2023Y9284), Natural Science Foundation of Jiangsu Province (BK20232020), State Key Laboratory of Analytical Chemistry for Life Science (5431ZZXM2408) and Excellent Research Program of Nanjing University (ZYJH004).

语种：英文

外文关键词：Cell immobilization - Cell membranes - Enzyme immobilization - Nafion membranes

摘要：Covalent modification of cell membranes has shown promise for tumor imaging and therapy. However, existing membrane labeling techniques face challenges such as slow kinetics and poor selectivity for cancer cells, leading to off-target effects and suboptimal in vivo efficacy. Here, we present an enzyme-triggered self-immobilization labeling strategy, termed E-SIM, which enables rapid and selective labeling of tumor cell membranes with bioorthogonal trans-cycloctene (TCO) handles in vivo. E-SIM utilizes P-TCO, an alkaline phosphatase (ALP) responsive quinone methide (QM) precursor with a TCO group, facilitating the rapid conjugation of high-density TCO handles onto tumor cell membranes via proximity labeling. These TCO groups then react efficiently with tetrazine (Tz)-bearing reporters via a fast bioorthogonal reaction, resulting in significant enrichment of reporters of various sizes and imaging modalities on tumor cell membranes. We demonstrate the efficacy of E-SIM labeling and bioorthogonal reaction for pretargeted multimodality imaging of tumors in vivo. Notably, we achieve selective and efficient installation of Tz-modified Renilla luciferase on tumor cells in vivo, thereby offering highly sensitive bioluminescence signals for detecting and guiding the surgical removal of small human HepG2 liver tumor peritoneal metastases. E-SIM represents a robust tool for precise tumor cell labeling in complex in vivo environments, feasible for pretargeted enrichment of various reporters in tumors for multimodal imaging applications.