Effects of radiofrequency exposure on in vitro blood-brain barrier permeability in the presence of magnetic nanoparticles

The blood-brain barrier (BBB) remains a major obstacle for the delivery of drugs in the treatment of many neurological diseases. In this study, we aimed to investigate the effects of radiofrequency electromagnetic fields (RF-EMFs) on the permeability of an in vitro BBB model under RF exposure alone, or in the presence of nanoparticles (NPs). For this purpose, an in vitro BBB model was established by seeding human umbilical vein endothelial cells (HUVECs) and human glioblastoma cell line (T98G) on the apical and basolateral sides of the transwell membrane, respectively. The integrity of the BBB model was confirmed by measuring transendothelial electrical resistance (TEER), and a fluorescein isothiocyanate (FITC)-dextran permeability assay was performed when the resistance reached 120 Ω cm². After the RF-field exposure (13.56 MHz, 80 W, 10 min), we found that FITC-dextran transported across the in vitro BBB was increased 10-fold compared to FITC-dextran transported without an RF-field. This notable phenomenon, which can be called the burst permeability RF effect (BP-RF), has been proposed for the first time in the literature. Subsequently, the effect of the RF-field on BBB permeability was also investigated in the presence of superparamagnetic iron oxide nanoparticles (SPIONs) and magnetic poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-b-PEG) nanoparticles (m-PNPs). It was found that the amount of both transported NPs on the basolateral sides increased after exposure to the RF-field. As a result, the RF-field can be applied simultaneously during treatment with clinical agents or nanocarriers, improving the permeability of the BBB, which may contribute to therapeutic efficacy of many drugs that are used in neurological diseases.