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

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/O-2 and depleting GSH under acidic condition. Besides, the released Cu2+ can contribute to T-1-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.

Automated summary

A photodynamic/chemodynamic synergistic therapeutic nanoagent, DCI, was synthesized to overcome the obstacles in tumor microenvironment by regulating the levels of H2O2, O2, and GSH. The DCI nanoagent can also be used for MRI imaging and achieve enhanced antitumor efficacy.