Injectable and Repeatable Inductive Heating of Iron Oxide Nanoparticle-Enhanced “PHIL” Embolic toward Tumor Treatment

Abstract

Deep-seated tumors of the liver, brain, and other organ systems often recur after initial surgical, chemotherapeutic, radiation, or focal treatments. Repeating these treatments is often invasive and traumatic. We propose an iron oxide nanoparticle (IONP)-enhanced precipitating hydrophobic injectable liquid (PHIL, MicroVention inc.) embolic as a localized dual treatment implant for nutrient deprivation and multiple repeatable thermal ablation. Following a single injection, multiple thermal treatments can be repeated as needed, based on monitoring of tumor growth/recurrence. Herein we show the ability to create an injectable stable PHIL-IONP solution, monitor deposition of the PHIL-IONP precipitate dispersion by μCT, and gauge the IONP distribution within the embolic by magnetic resonance imaging. Once precipitated, the implant could be heated to reach therapeutic temperatures >8 °C for thermal ablation (clinical temperature of ∼45 °C), in a model disk and a 3D tumor bed model. Heat output was not affected by physiological conditions, multiple heating sessions, or heating at intervals over a 1 month duration. Further, in ex vivo mice hind-limb tumors, we could noninvasively heat the embolic to an “ablative” temperature elevation of 17 °C (clinically 54 °C) in the first 5 min and maintain the temperature rise over +8 °C (clinically a temperature of 45 °C) for longer than 15 min.