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Magnetic hyperthermia is currently an EU-approved clinical therapy againsttumor cells that uses magnetic nanoparticles under a time varying magneticfield (TVMF). The same basic principle seems promising against trypanosomatidscausing Chagas disease and sleeping sickness, since therapeutic drugs availabledisplay severe side effects and drug-resistant strains. However, noapplications of this strategy against protozoan-induced diseases have beenreported so far. In the present study, Crithidia fasciculata, a widely usedmodel for therapeutic strategies against pathogenic trypanosomatids, wastargeted with Fe_{3}O_{4} magnetic nanoparticles (MNPs) in order to remotelyprovoke cell death using TVMFs. The MNPs with average sizes of d approx. 30 nmwere synthesized using a precipitation of FeSO_{4}4 in basic medium. The MNPswere added to Crithidia fasciculata choanomastigotes in exponential phase andincubated overnight. The amount of uploaded MNPs per cell was determined bymagnetic measurements. Cell viability using the MTT colorimetric assay and flowcytometry showed that the MNPs were incorporated by the cells with nonoticeable cell-toxicity effects. When a TVMF (f = 249 kHz, H = 13 kA/m) wasapplied to MNP-bearing cells, massive cell death was induced via anon-apoptotic mechanism. No effects were observed by applying a TVMF on control(without loaded MNPs) cells. No macroscopic rise in temperature was observed inthe extracellular medium during the experiments. Scanning Electron Microscopyshowed morphological changes after TVMF experiments. These data indicate (as aproof of principle) that intracellular hyperthermia is a suitable technology toinduce the specific death of protozoan parasites bearing MNPs. These findingsexpand the possibilities for new therapeutic strategies that combat parasiticinfections.

Application of magnetically induced hyperthermia on the model protozoan Crithidia fasciculata as a potential therapy against parasitic infections