RMF-Activated Superparamagnetic Iron Oxide Nanoparticles Trigger Macrophage-Dependent Protection Against Babesia microti Infection.

Babesiosis is an emerging tick-borne zoonosis hampered by drug-resistant Babesia parasites and the absence of vaccines. Rotating magnetic field-activated superparamagnetic iron oxide nanoparticles (RMF-SPIONs) exert anti-tumor and antibacterial effects, yet their efficacy against intraerythrocytic protozoa, including Babesia microti, is unclear. We established murine B. microti and Plasmodium yoelii infection models, using immunodeficient mouse strains and immune cell depletion approaches to dissect the antiparasitic mechanism, alongside cytokine detection, long-term physiological observation and parasite rechallenge assays. RMF-SPION therapy markedly inhibited B. microti proliferation but showed no efficacy against P. yoelii. Macrophages served as the key effector cells through IL-12 secretion, while NK cells likely played auxiliary regulatory roles in this system. Convalescent mice developed strain-specific premunition, though latent infection induced chronic inflammation and visceral lesions. In conclusion, RMF-SPIONs selectively activate macrophages to eliminate B. microti. Combining natural premunition with macrophage-targeted activation likely provides a non-chemical strategy against drug-resistant babesiosis.