Human Embryonic Kidney HEK293 Cells as a Model to Study SMVT-Independent Transport of Biotin and Biotin-Furnished Nanoparticles in Targeted Therapy.

The aim of this study was to investigate the usefulness of human embryonic kidney HEK293 cells as a model of normal cells in biotin-mediated therapy. The expression and role of sodium multivitamin transporter (SMVT) in the uptake and accumulation of free biotin, as well as cationic and neutral biotinylated PAMAM dendrimers of the fourth generation synthesized in our laboratory, were assessed in HEK293 cells in comparison to other immortalized (HaCaT) and cancer cells (HepG2, U-118 MG). The obtained data showed that a higher level of SMVT in HEK293 cells was not associated with a stronger uptake of biotin and biotinylated PAMAM dendrimers. Biotinylation increased the selective uptake of neutral dendrimers in an inversely proportional manner to the concentration used; however, the accumulation in HEK293 cells was lower than that in cells of other cell lines. The time-dependent biotin and biotinylated dendrimers uptake profiles differed significantly. Therefore, it should be assumed that the efficiency of biotinylated nanoparticles' uptake depends on multiple cellular transport mechanisms. Toxicity tests showed significantly higher sensitivity to PAMAM conjugates for HEK293 cells than for HepG2 and HaCaT cells. Molecular modeling studies and the profile of biotin uptake suggest that not only SMVT but also monocarboxylate transporter 1 (MCT-1) may play an important role in the selective transport of biotin and biotinylated nanoparticles into cells. Due to the complexity of the problem, further studies are necessary. In summary, HEK293 cells can be considered a valuable model of normal cells in the study of biotin- targeted therapy using nanoparticles based on PAMAM dendrimers.