Search

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 temperatures8 °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.

Vitrification can dramatically increase the storage of viable biomaterials in the cryogenic state for years. Unfortunately, vitrified systems ≥3 mL like large tissues and organs, cannot currently be rewarmed sufficiently rapidly or uniformly by convective approaches to avoid ice crystallization or cracking failures. A new volumetric rewarming technology entitled “nanowarming” addresses this problem by using radiofrequency excited iron oxide nanoparticles to rewarm vitrified systems rapidly and uniformly. Here, for the first time, successful recovery of a rat kidney from the vitrified state using nanowarming, is shown. First, kidneys are perfused via the renal artery with a cryoprotective cocktail (CPA) and silica‐coated iron oxide nanoparticles (sIONPs). After cooling at −40 °C min−1 in a controlled rate freezer, microcomputed tomography (µCT) imaging is used to verify the distribution of the sIONPs and the vitrified state of the kidneys. By applying a radiofrequency field to excite the distributed sIONPs, the vitrified kidneys are nanowarmed at a mean rate of 63.7 °C min−1. Experiments and modeling show the avoidance of both ice crystallization and cracking during these processes. Histology and confocal imaging show that nanowarmed kidneys are dramatically better than convective rewarming controls. This work suggests that kidney nanowarming holds tremendous promise for transplantation., Vitrification dramatically increases organ storage times in the cryogenic state beyond current storage limits. However, vitrified kidneys cannot currently be rewarmed sufficiently rapidly or uniformly to avoid ice crystallization or cracking failures. A new radiofrequency rewarming technology called “nanowarming” addresses this problem by exciting magnetic nanoparticles to rewarm vitrified kidneys rapidly and uniformly.