Activated Fluorescent Probe for Long‐Term Imaging and Surgical Navigation via Enzyme‐Mediated Fluorogenic Reaction and Self‐Assembly

作者：Ting Liu, Xiang Xia, Wenkai Liu, Chengyuan Lv, Chaogan Liu, Ran Wang, Jianjun Du, Jiangli Fan, Wen Sun, Xiaojun Peng · 发表于：Advanced Functional Materials · 年份：2025 · DOI：10.1002/adfm.202522069 · 被引用次数：3 · 研究领域：Nanoplatforms for cancer theranostics、Supramolecular Self-Assembly in Materials、Luminescence and Fluorescent Materials

Abstract Intraoperative fluorescence navigation is one of the most efficient and minimally invasive approaches for eliminating metastatic tumors in situ and poses minimal postoperative adverse effects. Therefore, a strategy combining enzyme responsiveness with in situ self‐assembly of small molecules can offer a promising approach for the precise removal of tumors. In this study, a fluorescence probe IHQA is reported for detecting and removing poorly vascularized metastatic foci via fluorescence guidance. The design of IHQA relies on the introduction of the solid‐state fluorophore, 6‐chloro‐2‐(2‐hydroxyphenyl) quinazolin‐4(3H)‐one (HPQ), which operates via an excited‐state intramolecular proton transfer (ESIPT) mechanism and plays a key role in enabling self‐assembly. Using Aminopeptidase N (APN) as a model target, it is demonstrated that overexpressed endogenous APN can activate this probe in tumor cells, resulting in the formation of nanoparticles ( IHQA‐nano ) that are directly endocytosed into lysosomes and can be visualized over the long term by fluorescence imaging. Simultaneous enhancements in signal‐to‐background ratio (>14) and in vivo duration (up to 72 h) enable real‐time, high‐sensitivity, high‐spatial‐resolution imaging, localization, and removal of very small (2 mm 3 ) metastatic foci. Overall, this method of tumor elimination via fluorescence intraoperative navigation is a potential tool for the real‐time diagnosis and navigation of different metastases.