Microwave-Responsive MnFe-Based Molybdenum Disulfide Nanoflowers for Enhanced Thermal-Dynamic-Chemo Synergistic Therapy in Bladder Cancer.

BACKGROUND

The most challenging clinical characteristic of bladder cancer (BC) is its exceptionally high recurrence rate. Recurrence, metastasis and drug resistance remain critical challenges in BC treatment. Microwave dynamic therapy (MWDT) is an emerging antitumor modality; however, its therapeutic efficacy is limited by the hypoxic tumor microenvironment (TME). To address these limitations, we developed a multifunctional nanoplatform (Mn-Fe-Dox-BSA-MoS2) to enhance oxygenation and therapeutic efficiency. In this system, MoS2 served as a microwave sensitizer and photoacoustic imaging (PAI) agent, while bovine serum albumin (BSA) improved biocompatibility. Doxorubicin (Dox) acted as a chemotherapeutic drug, Mn/Fe ion complexes provided catalase-like activity, and Cy5.5 enabled fluorescence imaging (FI).

METHODS

Reactive oxygen species (ROS) generation, oxygen production, imaging capability, and microwave/acid-responsive drug release were systematically evaluated. The antitumor efficacy and underlying mechanisms of Mn-Fe-Dox-BSA-MoS2-mediated therapy were further evaluated in MB49 cells in vitro and in BALB/c nude mice in vivo.

RESULTS

The nanoflowers exhibited excellent biosafety and efficient microwave sensitization, producing abundant ROS under MW irradiation. Dual-mode FI/PAI imaging enabled precise visualization of tumor accumulation. Mn/Fe complexes catalyzed H2O2 decomposition to continuously generate O2, alleviating tumor hypoxia and enhancing MWDT efficacy. Meanwhile, Dox was effectively delivered and released in response to MW irradiation and acidic TME conditions. The synergistic effects of chemotherapy, MWDT, and microwave thermotherapy (MWTT) significantly inhibited tumor cell proliferation.

CONCLUSION

Mn-Fe-Dox-BSA-MoS2 nanoflowers enable FI/PAI dual-modal imaging-guided multimodal therapy, demonstrating potent antitumor efficacy in a preclinical BC model.