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 MnFe 2 O 4 /TiVNbMoC 3 -cRGD (MXenes) nanocomposite for targeted photothermal- photodynamic therapy against bladder cancer. Methods: A multifunctional MXene-based nanocomposite was constructed by integrating MnFe 2 O 4 nanoparticles onto TiVNbMoC 3 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 MnFe 2 O 4 nanoparticles onto TiVNbMoC 3 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. A diagram showing the synthesis and application of MnFe2O4/TiVN bMoC3-cRGD for tumor treatment.The diagram illustrates the synthesis and application of MnFe2O4/TiVN bMoC3-cRGD. It begins with FeCl3·6H2O and MnCl2·4H2O, processed with NaOH at pH 12, 24 hours, 200 degrees Celsius and magnetic separation for 12 hours at 60 degrees Celsius, forming MnFe2O4. TiVN bMoAlC3 (MAX) is treated with 48 percent HF (400 rpm, 4 days, 55 degrees Celsius) to form TiVN bMoC3, then with 5 percent TMAOH (500 rpm, 4 hours, 55 degrees Celsius) to create TiVN bMoC3 (High-entropy). MnFe2O4 is combined with TiVN bMoC3 using chitosan (acetic acid) and glutaric dialdehyde, then Arg-Gly-Asp is added at 10 minutes, 60 degrees Celsius. The composite is activated with 880 nm light, increasing local temperature and reactive oxygen species, leading to apoptosis, immunogenic cell death and reduced tumor growth in mice with bladder tumors.