Predicting the Dominant Role of Dense Aggregates in Magnetic Hyperthermia via Intracellular‐Mimetic Nanoparticle Models

Dense aggregation of magnetic nanoparticles (MNPs) in cellular environments is a major contributor to reduced magnetic hyperthermia (MH) efficiency; however, in situ magnetic characterization remains challenging, necessitating reliable extracellular models to predict such behavior. In this study, soft and dense aggregates (≈200 nm) are engineered using 10 nm iron oxide MNPs, encapsulated in polymeric (soft) or inorganic (dense) shells, with morphological features and strong magnetic dipolar interactions confirming their similarity to nanoparticle assemblies found in living cells. Unlike previous studies that induced aggregation by modifying the surrounding medium, the approach enables controlled, invariant aggregation states, allowing systematic evaluation of the transition from soft to dense aggregation under both aqueous and high-viscosity, cell-mimicking conditions. Results demonstrate that dense aggregation leads to a >20% reduction in specific absorption rate (SAR), primarily due to decreased remanent magnetization (M_R), highlighting the critical role of aggregate structure. Viscosity is found to have a non-negligible effect once MNPs are aggregated, suggesting dominant Néel relaxation modulated by dipolar interactions. A strong SAR-M_R correlation is observed, while SAR-coercivity (H_C) dependence is disrupted by aggregation. These findings offer new insights for optimizing MH efficiency and guiding the design of magnetic nanoactuators for MH therapy.