Near‐Infrared Light‐Triggered MXene Nanocomposite for Tumor‐Specific Mild Photothermal‐Enhanced Chemodynamic Therapy

Abstract Mild photothermal therapy (PTT) is an emerging and elegant approach with minimal adverse effects, demonstrating itself as an effective treatment for cancer. However, potential challenges may arise from the overexpression of heat shock protein 90 (HSP90) and the reliance on monotherapy. Here, a near‐infrared (NIR) light‐triggered MXene nanocomposite (FA@MXene/CuO 2 /GA) is developed to synergistically combine mild PTT and chemodynamic therapy (CDT) for remarkably effective tumor eradication without any notable tissue damage. Under the irradiation of NIR light, the nanocomposite effectively enhances the mild PTT by suppressing HSP90 expression through the release of gambogic acid (GA) due to the excellent photothermal performance of Ti 3 C 2 MXene nanosheets as well as the tumor‐targeting ability and biocompatibility of the surface‐modified FA‐PEG‐SH. The copper‐based catalyst CuO 2 in this system releases Cu 2+ in an acid‐triggered manner within the tumor microenvironment, activating the Fenton‐like reaction to generate hydroxyl radicals, and the simultaneous production of H 2 O 2 serves to alleviate the deficiency of endogenous H 2 O 2 within the tumor. Overall, the current work showcases a remarkable synergistic anticancer effect of PTT and CDT, and also proposes new avenues for research in utilizing MXene nanomaterials for tumor treatment.