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

Yadong Liu,1,2,* Yaodong Chen,3,* Shazhou Ye,1,* Jiasheng Hu,1 Zhong Zheng,1 Kaining Lu,1 Wu Chen,3 Zejun Yan,1,4 Xingyi Li5 1Department of Urology, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 2State Key Laboratory of Ultrasound in Medicine and Engineering, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Ultrasonic Imaging, First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4Zhejiang Engineering Research Center of Innovative Technologies and Diagnostic and Therapeutic Equipment for Urinary System Diseases, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 5Department of Ultrasonic Imaging, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xingyi Li; Zejun Yan, Email [email protected]; [email protected]: 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. MoS subscript 2 is combined with Dox, Mn, Fe and BSA to form Mn-Fe-Dox-BSA-MoS subscript 2. This compound is shown interacting with a cell, enhancing MVDT, MWTT and chemotherapy, leading to tumor cell apoptosis. The process involves ROS enhancement. A mouse model is depicted, indicating the use of this compound for imaging and treatment, with PAI and imaging results shown. The overall process aims at effective tumor treatment and monitoring.Diagram of Mn-Fe-Dox-BSA-MoS2 for tumor treatment and imaging in a mouse model.Keywords: molybdenum disulfide, microwave dynamic therapy, microwave thermotherapy, chemotherapy, bladder cancer