A multifunctional mesoporous silica nanosystem for enhanced combinational photo-chemodynamic therapy via GSH depletion and •OH stabilization

A multifunctional mesoporous silica nanoplatform was constructed for synergistic photo-chemodynamic therapy. • WO 3-x adsorb hydroxyl radicals to enhance chemodynamic therapy, while Cu(II) depletes glutathione to reduce ROS scavenging and boost oxidative stress. • The nanoplatform achieves 80% in vitro cell inhibition and 73.9% in vivo tumor growth inhibition via synergistic PDT/CDT. Combination photo-chemodynamic therapy (PDT/CDT) represents a promising anticancer strategy that synergistically generates reactive oxygen species (ROS) through light activation and Fenton-like reactions. However, the therapeutic efficacy of ROS is often compromised by overexpressed glutathione (GSH) and the ultra-short lifetime of hydroxyl radicals (•OH). To address these challenges, we developed a novel mesoporous silica-based nanosystem integrating a Fenton catalyst Cu(II), oxygen-vacancy-rich tungsten oxide (WO 3-x ), and the photosensitizer zinc phthalocyanine. The nanosystem enhances oxidative damage through Cu(II)-mediated GSH depletion and WO 3-x -facilitated adsorption and stabilization of •OH via oxygen vacancy trapping, in addition to the synergistic PDT/CDT effect. Following conjugation with a mitochondria-targeting ligand, the nanosystem was evaluated in vitro and in vivo , achieving a cell inhibitory rate of 80% and a tumor growth inhibition rate of 73.9%, demonstrating high therapeutic efficacy. These results indicate that the as-synthesized multifunctional nanosystem with enhanced oxidative capacity holds great promise as a PDT/CDT nanoagent for tumor ablation. A mesoporous silica-based nanoplatform co-delivering Cu(II) Fenton catalyst, oxygen-deficient WO 3-x , and ZnPc photosensitizer with mitochondria-targeting TPP ligand achieves synergistic photo-chemodynamic therapy by depleting GSH, enhancing •OH and 1 O 2 production, and suppressing tumor growth by 73.9%. Download: Download high-res image (324KB) Download: Download full-size image