Multifunctional Nanozymes by Amplifying Intracellular Oxidative Stress for Enhanced Photothermal–Photodynamic Therapy

Due to the high efficiency and noninvasive nature, photodynamic therapy (PDT) and photothermal therapy (PTT) have received increasing attention as a potential tumor treatment approach. However, extreme hypoxia and overexpressed glutathione (GSH) in tumor cells restrict therapeutic efficacy. In this contribution, a multifunctional nanozyme of IR780-HCuS@MnO2 (I/C@M) was synthesized for tumor synergistic PPT and enhanced PDT. In the constructed nanozymes, hollow mesoporous copper sulfide (HCuS) as the core, the near-infrared dye IR780 iodide was loaded for PDT and PTT, and manganese dioxide (MnO2) was coated as a "gatekeeper" to prevent drug leakage on the surface. Under pH stimulation, MnO2 disintegrated to release IR780, producing exogenous reactive oxygen species (ROS) for PDT after under near-infrared (NIR) irritation. With the assistance of NIR, IR780 and HCuS can be used for PTT, and the double photothermal effect is higher than that of single therapy. In addition, MnO2 can amplify intracellular oxidative stress by depleting abundant GSH and H2O2 in the tumor, which will further enhance the PDT of IR780. Importantly, three treatments can be performed at the same time with only one laser irradiation. The excellent therapeutic effect of facilitating apoptosis and suppressing tumor growth was generally evaluated and validated both in vivo and in vitro. In summary, our work developed a potential nanomedicine for the synergistic treatment of breast cancer.