Copper Peroxides Based Multiple Tumor Microenvironment Regulation for Enhanced Photodynamic/Chemodynamic Synergistic Therapy

Abstract Hypoxia, overexpressed glutathione (GSH) and depletable H₂O₂ in tumor microenvironment (TME) are three major obstacles to the development of reactive oxygen species (ROS)‐mediated antitumor therapy. Herein, a photodynamic/chemodynamic synergistic therapeutic nanoagent, DMOS@CuO₂/ICG‐HA (DCI), is synthesized based on copper peroxide (CuO₂) and indocyanine green (ICG) co‐loaded disulfide‐bond‐incorporated dendritic mesoporous organosilica (DMOS), with modification of hyaluronic acid (HA). The DCI nanocomposites (NCs) can realize multiple TME regulating ability through releasing H₂O₂/O₂ and depleting GSH under acidic condition. Besides, the released Cu²⁺ can contribute to T₁‐weighted magnetic resonance imaging (MRI) in vitro and in vivo. After accumulating at the tumor sites, the DCI NCs can overcome the hypoxia and produce high level of ROS to induce cell apoptosis upon laser irradiation. Hence, the as‐prepared DCI nanoagent can realize MRI‐guided synergistic photodynamic/chemodynamic therapy with enhanced antitumor efficacy.