Abstract

Antitumor efficacy based on conventional chemodynamic therapy (CDT) is frequently constrained by insufficient endogenous H 2 O 2 and the limitations of monotherapy. Herein, we developed a metal-organic nanoplatform (CA-Fe NPs). This platform was fabricated through Fe 3+ -driven coordination assembly of artesunate (AS) and chlorin e6 (Ce6), facilitating preferential tumor accumulation via the enhanced permeability and retention (EPR) effect. Upon cellular internalization and 660 nm laser irradiation, the nanodrug enables a synergistic combination of Ce6-mediated photodynamic therapy (PDT) and AS-induced oxidative stress, which collaboratively amplifies intracellular reactive oxygen species (ROS) generation. This cascade induces mitochondrial membrane potential collapse, leading to extensive apoptotic cell death (77.5%). In a 4T1 tumor-bearing mouse model, this approach achieved marked tumor suppression with an excellent safety profile, offering a promising strategy for combination therapy. Graphical A Fe³+-coordinated artesunate/chlorin e6 nanoplatform enables tumor-targeted synergistic chemo/photodynamic therapy through glutathione (GSH)-triggered radical generation and laser-activated ROS production.