Receptor-targeted nanoparticles modulate cannabinoid anticancer activity through delayed cell internalization
Durán-Lobato, Dpto. Farmacia Y Tecnología Farmacéutica, Facultad De Farmacia, Universidad De Sevilla, Seville, Álvarez-Fuentes, Fernández-Arévalo, Martín-Banderas, C Prof. García González N, Matilde Durán-Lobato
Regarding previous works, the results of size and ZP of the plain PLGA NPs and THC-PLGA NPs here presented correlate with them11,17,18,19. The similar values of size and ZP of plain blank and plain THC-loaded PLGA formulations (PLGA NPs and THC-PLGA NPs) indicate a negligible drug adsorption of Δ9-THC onto the surface of NPs, being the majority of drug molecules incorporated into the NPs matrix11. Prior studies in our group presented a near 0% uptake values of NR-loaded plain PLGA NPs in Caco-2 cells in the first 6 h of incubation, that were increased at 24 h11. 4d) led to a similar general profile as with FITC tracking, albeit with differences in the obtained values at 1 h and 2 h. Given that the Tf internalization pathway through its Tf receptor involves the formation of clathrin-coated pits50,62,63, the results obtained supports that the delayed internalization observed for Tf-modified particles in standard conditions, potentially responsible for their enhanced antitumor effect, is due to a Tf-related cellular interaction. In addition, the higher intensity of fluorescence obtained in cells incubated with plain formulations vs. Tf-modified formulations (Fig.