Stress-Induced Gene Expression Sensing Intracellular Heating Triggered by Magnetic Hyperthermia

DE SOUSA,M.ELISA; CARREA, ALEJANDRA; MENDOZA ZÉLIZ, PEDRO; MURACA, DIEGO; MYKHAYLYK,OLGA; SOSA Y.E.; GOYA, R.G.; FRANCISCO H. SANCHEZ; DEWEY, RICARDO A.; FERNANDEZ VAN RAAP, MARCELA

JOURNAL OF PHYSICAL CHEMISTRY C

AMER CHEMICAL SOC

Lugar: Washington; Año: 2016 vol. 120 p. 7339 - 7348

1932-7447

It is known that alternating magnetic field applications oneukaryotic cells loaded with single domain iron oxide nanoparticles result inhigh hyperthermic cytotoxicity leading to cell death. Although magnetichyperthermia therapy for cancer tumors is being developed using this idea,some in vitro assays have shown controversial results indicating that an alternatingmagnetic field triggers a large apoptotic effect without significant culturetemperature increase. In agreement with these observations, a huge lowering innanoparticle specific heating rates, when going from the colloidal suspension tocell endosomes, together with cell death, has been reported. Here, we propose anew methodology to determine the occurrence of local heating in cells whenalternating magnetic fields in the radiofrequency field range are applied to cellcultures holding very low iron oxide concentrations, these concentrations beinginsufficient to produce a global cell culture temperature increase up to therapeuticvalues. To this end, human lung adenocarcinoma cells (A549 cell line) weretransduced with a lentiviral vector encoding the expression of the enhanced green fluorescence protein (EGFP) under the actionof the inducible human heat shock protein 70B promoter. This modified A549 cell line was incubated with aqueous suspensionsof magnetite core nanoparticles (uncoated or covered with coating agents like citric acid or silicon oxide) and exposed toradiofrequency fields. The application of an alternating magnetic field to cell cultures loaded with nanoparticles resulted in noglobal temperature increase but EGFP expression. Stress-inducible gene expression scales with uptake and nanoparticleproperties like saturation magnetization and heat dissipation efficiency. Our analysis demonstrates that EGFP expression is linkedto a localized intracellular temperature increase.