MXene/Doxorubicin Complex-Loaded Supramolecular Hydrogels for Near Infrared-Triggered Synergistic Cancer Therapy

Photothermal therapy (PTT) has attracted great interest due to the high spatial precision and reduced general toxicity compared to conventional cancer therapies. However, PTT often faces challenges such as incomplete tumor eradication and collateral damage to healthy tissues. Here, we report an injectable MXene-doxorubicin (MD) complex-loaded supramolecular hydrogel (MDGel) for dual synergistic cancer therapy of near-infrared (NIR) PTT and chemotherapy. MDGel is prepared by the host-guest interaction between gelatin-cyclodextrin (GE-CD) and hyaluronic acid-adamantane (HA-AD), facilitating the efficient dispersion of MD complexes in the hydrogel. NIR irradiation triggers the PTT and the release of doxorubicin with increasing temperature. In vitro therapeutic effect is confirmed by achieving nearly 80% cancer cell death via the synergistic effect, compared to the single-modality treatment. In vivo tumor inhibition (68.9% volume reduction) is further validated in skin cancer-bearing model mice with no substantial negative side effect. With its prolonged retention, NIR light-controlled release, and localized therapeutic effect, the MDGel system would provide a notable paradigm as a versatile platform for dual synergistic cancer therapy.