Magnetic-Powered Spora Lygodii Microrobots Loaded with Doxorubicin for Active and Targeted Therapy of Bladder Cancer

Qingxin Yang,1– 3 Wen Yuan,2 Tinghui Zhao,4 Yanixao Jiao,5 Menghuan Tang,5 Zhaoqing Cong,5,6 Song Wu6 1Department of Pharmacy, Mianyang Orthopaedic Hospital, Mianyang, 621000, People’s Republic of China; 2Mianyang Key Laboratory of Development and Utilization of Chinese Medicine Resources, Mianyang, 621000, People’s Republic of China; 3The Third Affiliated Hospital of Shenzhen University, Shenzhen Luohu People’s Hospital, Shenzhen, 518000, People’s Republic of China; 4Department of Burns and Plastic Surgery, Mianyang Central Hospital, Mianyang, 621000, People’s Republic of China; 5Department of Biochemistry and Molecular Medicine, University of California, Davis, CA, 95817, USA; 6South China Hospital, Medical School, Shenzhen University, Shenzhen, 518116, People’s Republic of ChinaCorrespondence: Song Wu; Zhaoqing Cong, Email [email protected]; [email protected] and Purpose: Bladder cancer has high recurrence rates despite standard treatments, necessitating innovative therapeutic approaches. This study introduces magnetically powered microrobots utilizing Traditional Chinese Medicine (TCM) Spora Lygodii (SL) encapsulated with Doxorubicin (DOX) and Fe3O4 nanoparticles (Fe/DOX@SL) for targeted therapy.Methods: Fe3O4 nanoparticles were synthesized via co-precipitation and combined with SL spores and DOX through dip-coating to form Fe/DOX@SL microrobots. Their propulsion was controlled by a rotating magnetic field (RMF) for precise delivery. The microrobots’ mobility and adherence were assessed in various biological media. Therapeutic efficacy was evaluated using an orthotopic bladder cancer model in mice treated intravesically with Fe/DOX@SL under RMF guidance, compared to controls.Results: Fe/DOX@SL microrobots demonstrated efficient movement and stable navigation in biological environments. In vivo experiments showed superior retention in the bladder, prolonged adherence to the mucosa, and significantly enhanced tumor suppression in the RMF-guided group. Bioluminescence imaging confirmed reduced tumor growth, and histological analysis revealed substantial tumor regression compared to other treatments.Discussion and Conclusion: This study highlights the potential of integrating TCM with advanced microrobotics. The biocompatible Fe/DOX@SL microrobots leverage SL’s therapeutic properties and fuel-free magnetic control to overcome challenges in bladder cancer treatment, such as poor drug retention and off-target toxicity. This novel platform represents a promising advancement in targeted cancer therapy. The innovative fusion of TCM and microrobotics introduces a potent, targeted therapeutic strategy for bladder cancer, paving the way for broader biomedical applications.Keywords: Traditional Chinese Medicine (TCM), Spora Lygodii, microrobots, bladder cancer