Nanoparticle-mediated magnetic hyperthermia for ectopic pregnancy treatment.

Magnetic hyperthermia (≤45 °C) is a promising strategy for conditions requiring localized tissue disruption in sensitive anatomical regions, including ectopic pregnancy (EP), where temperature-sensitive trophoblasts can be selectively disrupted by modest heating. However, effective treatment requires nanoparticles that rapidly reach therapeutic temperatures after systemic administration while attenuating heat generation as the target temperature is approached to minimize damage to surrounding tissues. Here, cobalt-doped soft ferromagnetic iron oxide nanoparticles (Co-FIONs) were engineered to achieve this balance through classic temperature-dependent coercivity within the hyperthermia window. Coercivity decreased 2.27-fold at 45 °C, accompanied by a 1.58-fold reduction in heating rate from 1.9 to ∼1.2 °C s-1, progressively attenuating heat generation while maintaining a high specific absorption rate (SAR) of 2907 ± 84 W g-1 Fe. Box-Lucas analysis further demonstrated progressive temperature-dependent attenuation of heating kinetics, consistent with the combined effects of magnetic softening and thermal dissipation. Under biologically relevant conditions, Co-FIONs@PP retained a high SAR of 474 ± 56 W g-1 Fe in 2.5% agar, demonstrating its ability to achieve therapeutically relevant magnetic hyperthermia at clinically feasible iron doses. Systemically administered Co-FIONs@PP also provided T2/T2*-weighted MRI contrast for localization of implantation sites. In pregnant mice, Co-FIONs@PP accumulated at fetoplacental units and, following two alternating magnetic field exposures, induced localized trophoblast apoptosis and selective gestational sac disruption while preserving adjacent endometrium and subsequent fertility. These findings establish Co-FIONs@PP as a promising theranostic platform for MRI visualization and localized magnetic hyperthermia, providing a foundation for minimally invasive, image-assisted treatment of EP.