Progress in the design of nanoscale magnets for localized hyperthermia cancer therapy has been largely driven by trial-and-error approaches, for instance, by changing of the stoichiometry composition, size, and shape of the magnetic entities. So far, widely different and often conflicting heat dissipation results have been reported, particularly as a function of the nanoparticle concentration. Thus, achieving hyperthermia-efficient magnetic ferrofluids remains an outstanding challenge. Here we demonstrate that diverging heat-dissipation patterns found in the literature can be actually described by a single picture accounting for both the intrinsic magnetic features of the particles (anisotropy, magnetization) and experimental conditions (concentration, magnetic field). Importantly, this general magnetic-hyperthermia scenario also predicts a novel non-monotonic concentration dependence with optimum heating features, which we experimentally confirmed in iron oxide nanoparticle ferrofluids by fine-tuning the particle size. Overall, our approach implies a magnetic hyperthermia trilemma that may constitute a simple strategy for development of magnetic nanomaterials for optimal hyperthermia efficiency.

Magnetic nanoparticles exposed to alternating magnetic fields have shown a great potential acting as magnetic hyperthermia mediators for cancer treatment. However, a dramatic and unexplained reduction of the nanoparticle magnetic heating efficiency has been evidenced when nanoparticles are located inside cells or tissues. Recent studies suggest the enhancement of nanoparticle clustering and/or immobilization after interaction with cells as possible causes, although a quantitative description of the influence of biological matrices on the magnetic response of magnetic nanoparticles under AC magnetic fields is still lacking. Here, we studied the effect of cell internalization on the dynamical magnetic response of iron oxide nanoparticles (IONPs). AC magnetometry and magnetic susceptibility measurements of two magnetic core sizes (11 and 21 nm) underscored differences in the dynamical magnetic response following cell uptake with effects more pronounced for larger sizes. Two methodologies have been employed for experimentally determining the magnetic heat losses of magnetic nanoparticles inside live cells without risking their viability as well as the suitability of magnetic nanostructures for in vitro hyperthermia studies. Our experimental results-supported by theoretical calculations-reveal that the enhancement of intracellular IONP clustering mainly drives the cell internalization effects rather than intracellular IONP immobilization. Understanding the effects related to the nanoparticle transit into live cells on their magnetic response will allow the design of nanostructures containing magnetic nanoparticles whose dynamical magnetic response will remain invariable in any biological environments, allowing sustained and predictable in vivo heating efficiency.

Iron oxide nanoparticles have found an increasing number of biomedical applications as sensing or trapping platforms and therapeutic and/or diagnostic agents. Most of these applications are based on their magnetic properties, which may vary depending on the nanoparticle aggregation state and/or concentration. In this work, we assess the effect of the inter- and intra-aggregate magnetic dipolar interactions on the heat dissipation power and AC hysteresis loops upon increasing the nanoparticle concentration and the hydrodynamic aggregate size. We observe different effects produced by inter- (long distance) and intra-aggregate (short distance) interactions, resulting in magnetizing and demagnetizing effects, respectively. Consequently, the heat dissipation power under alternating magnetic fields strongly reflects such different interacting phenomena. The intra-aggregate interaction results were successfully modeled by numerical simulations. A better understanding of magnetic dipolar interactions is mandatory for achieving a reliable magnetic hyperthermia response when nanoparticles are located into biological matrices.

In the pursuit of controlling the heat exposure mediated by magnetic nanoparticles, we provide new guidelines for tailoring magnetic relaxation processes via dipolar interactions. For this purpose, highly crystalline and monodisperse magnetic iron oxide nanocrystals whose sizes range from 7 to 22 nm were synthesized by thermal decomposition of iron organic precursors in 1-octadecene. The as-synthesized nanoparticles are soft nanomagnets, showing superparamagnetic-like behavior and SAR values which progressively increase with particle size, field frequency, and amplitude up to 3.6 kW/g Fe . Our data show the influence of media viscosity, particle size, and concentration on dipolar interactions and consequently on the magnetic relaxation processes related to the heat release. Understanding the role of dipolar interactions is of great importance toward the use of iron oxide nanoparticles as efficient hyperthermia mediators.

Hysteresis losses in magnetic nanoparticles constitute the basis of magnetic hyperthermia for delivering a local thermal stress. Nevertheless, this therapeutic modality is only to be realised through a careful appraisal of the best possible intrinsic and extrinsic conditions to the nanoparticles for which they maximise and preserve their heating capabilities. Low frequency (100 kHz) hysteresis loops accurately probe the dynamical magnetic response of magnetic nanoparticles in a more reliable manner than calorimetry measurements, providing conclusive quantitative data under different experimental conditions. We consider here a set of iron oxide or cobalt ferrite nanocubes of different sizes, through which we experimentally and theoretically study the influence of the viscosity of the medium on the low frequency hysteresis loops of magnetic colloids, and hence their ability to produce and dissipate heat to the surroundings. We analyse the role of nanoparticle size, size distribution, chemical composition, and field intensity in making the magnetisation dynamics sensitive to viscosity. Numerical simulations using the stochastic Landau-Lifshitz-Gilbert equation model the experimental observations in excellent agreement. These results represent an important contribution towards predicting viscosity effects and hence to maximise heat dissipation from magnetic nanoparticles regardless of the environment.