Harnessing a cRGD-Targeted Schottky Junction MXene Nanocomposite for Potent Bladder Cancer Therapy: Dual-Modal PTT/PDT Effects with Immune Activation and Favorable Comparison to Doxorubicin

Objective This study developed a multifunctional MnFe2O4/TiVNbMoC3-cRGD (MXenes) nanocomposite for targeted photothermal- photodynamic therapy against bladder cancer.Methods A multifunctional MXene-based nanocomposite was constructed by integrating MnFe2O4 nanoparticles onto TiVNbMoC3 MXene nanosheets to form a layer-on-layer Schottky junction, followed by conjugation of cRGD peptides for tumor targeting. Successful synthesis, colloidal stability, broad optical absorption, efficient photothermal conversion and ROS generation under 808 nm laser were confirmed. In vitro assays were conducted using 5637 bladder cancer cells, and a murine bladder tumor model was established to evaluate the anticancer efficacy. Biocompatibility assessments were also carried out.Results The composite was constructed by integrating MnFe2O4 nanoparticles onto TiVNbMoC3 MXene nanosheets, which formed a layer - on - layer Schottky junction. Then, cRGD peptides were conjugated to the surface for tumor targeting. Comprehensive characterization confirmed successful synthesis, favorable colloidal stability, broad optical absorption, and efficient photothermal conversion and reactive oxygen species (ROS) generation under 808 nm laser irradiation. In vitro, the cRGD-targeted nanocomposite was efficiently internalized by 5637 bladder cancer cells and showed significantly higher anticancer efficacy than doxorubicin (DOX), including inhibition of proliferation, migration, colony formation, and induction of apoptosis and immunogenic cell death. In a murine bladder tumor model, the nanocomposite achieved the strongest tumor growth suppression and reduced final tumor volume more effectively than DOX. Biocompatibility assessments showed minimal hemolysis and no major organ damage at therapeutic doses.Conclusion This MXene-based Schottky junction nanocomposite represents a promising targeted platform for dual-modal photothermal/photodynamic therapy combined with immune activation in bladder cancer, warranting further translational investigation.