Biodegradable Radiofrequency Responsive Nanoparticles For Augmented Thermal Ablation Combined With Triggered Drug Release In Liver Tumors

Radiofrequency ablation (RFA) and doxorubicin (Dox) chemotherapy are separately approved for liver cancer therapy; however, both have limited success in the clinic due to suboptimal/nonuniform heating and systemic side effects, respectively. Here, we report a biodegradable nanoparticle (NP) system showing excellent RF hyperthermic response together with the ability to locally deliver Dox in the liver under RF trigger and control. The nanosystem was prepared by doping a clinically permissible dose (similar to 4.3 wt %, 0.03 ppm) of stannous ions in alginate nanoparticles (similar to 100 nm) coloaded with Dox at similar to 13.4 wt % concentration and surface conjugated with galactose for targeting asialo-glycoprotein receptors in liver tumors. Targeted NP-uptake and increased cytotoxicity when combined with RF exposure was demonstrated in HEPG2 liver cancer cells. Following in vitro (chicken liver phantom) demonstration of locally augmented RF thermal response, in vivo scintigraphic imaging of Tc-99-labeled NPs was performed to optimize liver localization in Sprague Dawley (SD) rats. RF ablation was performed in vivo using a cooled-tip probe, and uniformly enhanced (similar to 44%) thermal ablation was demonstrated with magnetic resonance imaging along with RF-controlled Dox release. In orthotopic rat liver tumor models, real-time infrared imaging revealed significantly higher (similar to 20 degrees C) RF thermal response at the tumor site, resulting in uniform augmented ablation (similar to 80%) even at a low RF power exposure of 15 W for just 1 min duration. Being a clinically acceptable, biodegradable material, alginate nanoparticles hold strong translational potential for augmented RF hyperthermia combined with triggered drug release.