Thermoresponsive Magnetic Hydrogel for Local Thermal Ablation Treatment of Rectal Cancer

Thermal ablation treats cancer by raising local tumor temperature above ∼50 °C to induce coagulative necrosis. However, current approaches are invasive, as they typically require needle-like applicators to deliver thermal energy directly into the tumor. In this study, a magnetic hydrogel was developed as a noninvasive strategy for localized rectal cancer ablation aimed at preoperative tumor downsizing. The formulation comprises superparamagnetic iron oxide nanoparticles (SPIONs: Mn_0.6Zn_0.4Fe₂O₄) dispersed in Pluronic F127 (PF127). PF127 confers thermoresponsive sol-gel behavior at physiological temperature: upon contact with tissue, the formulation rapidly gels and becomes immobilized at the application site, minimizing spread to adjacent healthy tissue. After gel placement, an alternating magnetic field (AMF) is applied externally to activate the SPIONs to generate heat <i>in situ</i>, inducing local thermal ablation at the disease site. The gel can be administered either by syringe injection or by topical application, depending on tumor geometry. Adding SPIONs to the PF127 matrix did not alter the critical gelation temperature (CGT, 27.7 °C) but increased gel hardness and adhesiveness. When exposed to a 14 mT AMF at 596.2 kHz, the magnetic hydrogel exhibited excellent heating performance, reaching temperatures above the thermal ablation threshold (50 °C) within 3 min. The thermal ablation efficacy of the magnetic hydrogel was evaluated both <i>ex vivo</i> and <i>in vivo</i> using colorectal cancer xenograft mouse models. <i>Ex vivo</i> studies showed that a 15 min thermal ablation treatment resulted in an immediate 30% reduction in tumor volume. <i>In vivo</i>, a more pronounced effect was observed, with tumor volume decreased 69% 2 days after a single 20 min treatment. The finding highlighted the potential of the magnetic hydrogel as an alternative treatment for localized rectal cancer, either for preoperative tumor down-sizing or in cases where standard therapies such as surgery or chemo-radiotherapy are not feasible.