Chen, Yu-LiangYu-LiangChenLiu, Ming-HsinMing-HsinLiuHsieh, Ming-FengMing-FengHsiehLiang, Yung-YiYung-YiLiangLin, Che-WeiChe-WeiLinChuang, Er-YuanEr-YuanChuangWu, Kevin C.-W.Kevin C.-W.WuJIASHING YU2025-12-182025-12-18202521922640https://www.scopus.com/record/display.uri?eid=2-s2.0-105021362347&origin=resultslisthttps://scholars.lib.ntu.edu.tw/handle/123456789/734768Thrombosis remains a leading cause of mortality worldwide; however, current thrombolytic therapies suffer from limited thrombus targeting, poor penetration, and systemic side effects. To address these challenges, a fibrin-targeting photothermal nanoassembly, GCREKA-Pd@MIL-100, is engineered by encapsulating ultrasmall palladium (Pd) nanoclusters into a MIL-100(Fe) metal–organic framework and grafting a stabilized peptide ligand Gly–Cys–Arg–Glu–Lys–Ala (GCREKA) onto its surface. The porous MIL-100 matrix provides spatial confinement for the Pd nanoclusters, yielding uniform localized surface plasmon resonance (LSPR) active domains with high near-infrared (NIR) photothermal conversion efficiency. Covalent functionalization with GCREKA enhances colloidal stability and thrombus affinity. In vitro studies demonstrate that GCREKA-Pd@MIL-100 exhibits excellent cytocompatibility and hemocompatibility while achieving a clot mass reduction of over 50% under NIR irradiation. In a FeCl3-induced mouse mesenteric thrombosis model, GCREKA-Pd@MIL-100 accumulates selectively at the thrombotic site accompanied by localized heat (>60 °C) generation and achieves ≈60% thrombus clearance without off-target tissue damage. These findings highlight that GCREKA-Pd@MIL-100 is a potent site-specific nanoagent for minimally invasive thrombolysis, offering a promising alternative to conventional thrombolytic therapies.falsefibrin targetingnanomedicinephotothermal therapythrombolytic therapy[SDGs]SDG3journal article10.1002/adhm.2025033942-s2.0-105021362347