Supramolecular poly(vinyl alcohol)-folate structure as functional layer and colloidal stabilizer of poly(vinyl acetate) nanoparticles with potential use as nanocarrier for hydrophobic antitumor agents

摘要

Poly(vinyl acetate) nanoparticles 50 +/- 20 nm in diameter were synthesized by emulsion polymerization using poly(vinyl alcohol) (PVA) as stabilizer, loaded with eugenol and physically functionalized with folate in a post-reaction step. Interfacial tension and zeta potential measurements were done to provide evidence about the association between PVA and folate. In order to obtain the target particle size, the effect of the PVA molar mass on the colloidal stability of the latex was studied. The cytotoxic effect of these NPs was evaluated in vitro in the breast triple-negative cancer cell line MDA-MB-231, and an apoptosis/necrosis assay by flow cytometry was carried out. The capability of the nanocarrier to increase the production of reactive oxygen species in cancer cells was determined by flow cytometry. Nanotoxicological assessments of the NPs revealed that unloaded NPs were not cytotoxic, that functionalized-loaded NPs induced a decrease in cell viability by up to 70%, and that they induced apoptosis of breast cancer cells due to oxidative stress damage. Cytotoxicity significantly decreased in the absence of folate, suggesting the success of the physical functionalization in the receptor-mediated drug delivery mechanism.