MNP-based Magnetothermal Therapy Scheme

Abstract

This dissertation explores the in vivo therapeutic potential of magnetic nanoparticles (MNPs) by leveraging their ability to generate heat when exposed to alternating magnetic fields (AMF). The research focuses on three key applications: magnetic hyperthermia for cancer treatment, magnetothermal brain stimulation for post- stroke functional recovery, and thermal estimation using magnetic particle imaging (MPI). Together, these studies aim to establish a comprehensive framework for magnetothermal therapy. In the first topic, the physicochemical characteristics of various MNPs were thoroughly analyzed. These characteristics include core size, hydrodynamic diameter, magnetic behavior, and saturation magnetization. The analysis was conducted to predict thermal performance and determine optimal injection concentrations for in vivo applications. Among the tested nanoparticles, Synomag-D exhibited superior properties, making it the most suitable for in vivo applications. In the second topic, magnetic fluid hyperthermia was applied to cancer therapy. A simulation-guided dosing strategy was developed based on tumor geometry. Using a pancreatic tumor mouse model, it was found that thermal retention strongly depends on tumor size. A critical tumor volume was identified, above which a volume-normalized injection strategy was effective, while smaller tumors required a minimum injection approach. These results underscore the importance of personalized dosing strategies to ensure effective and consistent hyperthermia. In the third topic, magnetothermal brain stimulation was explored for stroke therapy. Focused magnetic stimulation was applied to the penumbra region to promote functional recovery, representing the first demonstration of non-invasive motor restoration via magnetothermal methods. Simulation and in vivo validation confirmed localized heating, TRPV1 channel activation, and increased blood–brain barrier (BBB) permeability. This method allowed precise, region-specific stimulation with minimal systemic impact, demonstrating strong potential for neuromodulation and stroke rehabilitation. In the final topic, MPI was employed to estimate MNP concentration and temperature in deep brain regions, enabling near real-time thermal monitoring. MPI revealed that MNPs remained localized at the stimulation site for up to 72 hours, supporting repeatable and sustained heating. The observed temperature reached 40 ℃, satisfying the thresholds required for both TRPV1 activation and BBB modulation. These findings highlight MPI's utility in guiding the spatiotemporal control of therapeutic heating. Collectively, this work presents a novel MNP-based theranostic platform that integrates localized heating, functional stimulation, and non-invasive temperature monitoring. The proposed approach offers a promising pathway toward personalized, image-guided, and non-invasive nanotherapies across various clinical applications. ©2025 Kim, HoHyeon ALL RIGHTS RESERVED