Tumor Size-Dependent Magnetic Hyperthermia Efficiency: A Simulation-Guided In Vivo Study

Abstract

Magnetic hyperthermia has shown promise as a localized cancer treatment, but optimizing the injection dose of magnetic nanoparticles (MNPs) remains a major challenge, particularly in tumors with different sizes. In this study, we present a simulation-guided and in vivo validated framework for injection dose planning based on the tumor volume. Specific loss power (SLP) of PEG-coated Synomag-D MNPs was estimated under immobilized conditions using tissue-mimicking agarose phantoms and incorporated into a three-dimensional COMSOL model of pancreatic tumors. Simulations were conducted for a wide range of tumor sizes (80-700 mm3) to identify the required MNP concentration to reach therapeutic temperatures (45 degrees C). The results revealed a nonlinear relationship between the tumor volume and required MNP amount, characterized by a critical size that separates two treatment regimes: small tumors requiring a minimum injection (MI) to compensate for high relative heat loss and large tumors where dose scales linearly with volume-Tumor Volume-Normalized Injection (TVNI). This two-regime hypothesis was validated in vivo using 31 pancreatic tumor mouse models divided into five groups. Complete tumor regression was achieved in groups treated with appropriately matched dosing strategies, while a mismatched protocol failed to reach therapeutic temperatures. With further analysis, we linked the critical size to fundamental thermal diffusion limits, which provided a theoretical basis for defining dosing strategies based on tumor volume. Our findings underscore the need for size-specific dosing strategies, which are necessary and offer practical insights into tailoring MNP dosing for improved treatment outcomes, particularly for early stage or small-volume tumors that are known to be difficult to treat. However, regardless of the tumor size or type, minimizing the injection dose is always desirable for biosafety, and our findings further highlight the importance of enhancing MNPs' SLP by tuning their intrinsic magnetic properties-particularly to meet the disproportionate demands of small tumors without compromising safety.