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Magnetic fluid hyperthermia (MFH), the procedure of raising the temperatureof tumor cells using magnetic nanoparticles (MNPs) as heating agents, hasproven successful in treating some types of cancer. However, the low heatingpower generated under physiological conditions makes necessary a high localconcentration of MNPs at tumor sites. Here, we report how the in vitro heatingpower of magnetically soft MnFe$_2$O$_4$ nanoparticles can be enhanced byintracellular low-dimensional clusters through a strategy that includes: a) thedesign of the MNPs to retain N\'eel magnetic relaxation in high viscositymedia, and b) culturing MNP-loaded cells under magnetic fields to produceelongated intracellular agglomerates. Our direct in vitro measurementsdemonstrated that the specific loss power (SLP) of elongated agglomerates($SLP=576\pm33$ W/g) induced by culturing BV2 cells in situ under a dc magneticfield was increased by a factor of 2 compared to the $SLP=305\pm25$ W/gmeasured in aggregates freely formed within cells. A numerical mean-field modelthat included dipolar interactions quantitatively reproduced the SLPs of theseclusters both in phantoms and in vitro, suggesting that it captures therelevant mechanisms behind power losses under high-viscosity conditions. Theseresults indicate that in situ assembling of MNPs into low-dimensionalstructures is a sound possible way to improve the heating performance in MFH.

acs applied nano materials

Low Dimensional Assemblies of Magnetic MnFe$_2$O$_4$ Nanoparticles and  Direct In Vitro Measurements of Enhanced Heating Driven by Dipolar  Interactions: Implications for Magnetic Hyperthermia