Iron Oxide Nanozyme for Magnetothermal Activation of ER-TRPV1 Enables Efficient Intravesical Therapy of Bladder Cancer

Drug-mediated intravesical therapy is a widely used treatment approach for bladder cancer (BCa), which is limited by poor tumor accumulation and the toxicity of drugs. Herein, a facile approach utilizing magnetic hyperthermia therapy (MHT) for BCa treatment is reported through intravesical instillation of tumor-targeting iron oxide nanoparticles (IONPs), which are coated with anti-FGFR3 antibodies for specific binding to FGFR3 overexpressed on BCa cells. The antibody coating significantly enhanced targeting ability and increased cancer cell uptake. Under an alternating magnetic field (AMF), the IONPs magnetothermally activated TRPV1 on the endoplasmic reticulum (ER) of BCa and induced Ca2+ overload in RT4 BCa cells. The magnetothermal treatment significantly upregulated the pro-apoptotic gene expression of Bax, Pro-caspase-3, and Cytc in RT4 cells, and downregulated the anti-apoptotic effector gene Bcl-2, ultimately causing augmented apoptosis in cancer cells. The application of intravesical FGFR3-targeting MHT successfully resulted in greater suppression of tumor growth and improved survival rate of mice, compared to the control, IONP, and AMF-treated groups. These results hold significant potential as a transformative modality toward BCa therapeutic application.