Thermal‐Responsive MXene‐DNA Hydrogel for Near‐Infrared Light Triggered Localized Photothermal‐Chemo Synergistic Cancer Therapy

Abstract Stimuli‐responsive DNA hydrogels are promising candidates for cancer treatment, as they not only possess biocompatible and biodegradable 3D network structures as highly efficient carriers for therapeutic agents but also are capable of undergoing programmable gel‐to‐solution transition upon external stimuli to achieve controlled delivery. Herein, a promising platform for highly efficient photothermal‐chemo synergistic cancer therapy is established by integrating DNA hydrogels with Ti 3 C 2 T X ‐based MXene as a photothermal agent and doxorubicin (DOX) as a loaded chemotherapeutic agent. Upon the irradiation of near‐infrared light (NIR), temperature rise caused by photothermal MXene nanosheets triggers the reversible gel‐to‐solution transition of the DOX‐loaded MXene‐DNA hydrogel, during which the DNA duplex crosslinking structures unwind to release therapeutic agents for efficient localized cancer therapy. Removal of the NIR irradiation results in the re‐formation of DNA duplex structures and the hydrogel matrix, and the recombination of free DOX and adaptive hydrogel transformations can also be achieved. As demonstrated by both in vitro and in vivo models, the MXene‐DNA hydrogel system, with excellent biocompatibility and injectability, dynamically NIR‐triggered drug delivery, and enhanced drug uptake under mild hyperthermia conditions, exhibits efficient localized cancer treatment with fewer side effects to the organisms.