The influence of cell and nanoparticle properties on heating and cell death in a radiofrequency field

摘要

The use of non-invasive radiofrequency (RF) energy to induce mild thermal and non-thermal effects in cancer tissue is under study as an adjuvant to chemo, radio or immuno therapy. This study examines cell specific sensitivities to RF exposure and the potential of nanoparticles to elevate heating rates or enhance biological effects. Increases in the heating rate of water in an RF field operating at 13.56 MHz (0.004-0.028 degrees C/s) were positively correlated with concentration of hybrid nanoparticles (1-10 mg/ml) consisting of water soluble malonodiserinolamide [60]fullerene (C-60-ser) conjugated to the surface of mesoporous silica nanoparticles (SiO2-C-60). The heating rate of highly conductive cell culture media (0.024 degrees C/s) was similar to that of the highest concentration of nanoparticles in water, with no significant increase due to addition of nanoparticles at relevant doses (<100 mu g/ml). With respect to cell viability, anionic (SiO2 and SiO2-C-60) or neutral (C-60) nanoparticles did not influence RF-induced cell death, however, cationic nanoparticles (4-100 mu g/ml) caused dose-dependent increases in RF-induced cell death (24-42% compared to RF only). The effect of cell type, size and immortalization on sensitivity of cells to RF fields was examined in endothelial (HUVEC and HMVEC), fibroblast (primary dermal and L939) and cancer cells (HeLa and 4T1). While the state of cellular immortalization itself did not consistently influence the rate of RF-induced cell death compared to normal cell counter parts, cell size (ranging from 7 to 30 mu m) negatively correlated with cell sensitivity to RF (21-97% cell death following 6 min irradiation). In summary, while nanoparticles do not alter the heating rate of biologically-relevant solutions, they can increase RF-induced cell death based on intrinsic cytotoxicity; and cells with smaller radii, and thereby greater surface membrane, are more susceptible to cell damage in an RF field than larger cells.