Cell Uptake Enhancement of Folate Targeted Polymer Coated Magnetic Nanoparticles

Dual targeted drug delivery systems represent a potential platform for developing efficient vector to tumor sites. In thisstudy we evaluated a folate- and magnetic-targeted nanocarriers based on 10 nm iron oxide nanodomais coated with theproperly synthesized and characterized folic acid (FA)-functionalized amphiphilic copolymer PHEA-PLA-PEG-FA. FA waschemically conjugated to one end of diamino-polyethylene glycol of 2000 Da, in order to ensure its exposition on thepolymer coated magnetic nanoparticles (MNPs-FA). The prepared nanoparticles have been exhaustively characterized bydifferent methods, including DLS, SEM, FT-IR and magnetic measurements. Magnetic nanoparticles showed dimensionof about 37 nm with a narrow size distribution and a characteristic superparamagnetic behaviour. The lack of cytotoxicityof MNPs-FA and MNPs was assessed both on MCF7 cells, used as a model tumor cell line, and on 16HBE, used asnormal human cell model, by evaluating cell viability using MTS assay, while the preferential internalization of MNPs-FAinto tumor cells rather that into normal cells was confirmed by the quantization of internalized iron oxide. Uptake studieswere also performed in the presence of a permanent magnet in order to verify the synergistic effect of magnetic field inenhancing the internalization of magnetic nanoparticles. Finally, real-time confocal microscopy experiments were carriedout to further confirmed that FA ligand enhances the MNPs-FA accumulation into cancer cell cytoplasm.