Folic acid-decorated PEGylated magnetite nanoparticles as efficient drug carriers to tumor cells overexpressing folic acid receptor

Abstract

The improved drug delivery systems (DDS) are needed for the targeted delivery of their therapeutic cargo (biologically active protein/peptide molecules, nucleic acids, vaccines, etc.) to diseased cells. Thus, we aimed to develop magnetite nanoparticles (Fe₃O₄), stabilized with polyethylene glycol (PEG) and decorated (surface-functionalized) with folic acid (FA) (Fe₃O₄@PEG@FA) to ensure targeted internalization in cells expressing the folic acid receptors (FR). The Fe₃O₄@PEG@FA nanoparticles were synthesized by co-precipitation in a one-pot methodology. Curcumin (Curc), a polyphenol with anti-tumoral activity, was loaded on the nanoparticles, and FA-targeted (Fe₃O₄@PEG@FA@Curc) and non-targeted (Fe₃O₄@PEG@Curc) systems were obtained. The internalization of Fe₃O₄@PEG@FA@Curc and Fe₃O₄@PEG@Curc nanoparticles was determined in two tumor cell lines, the FR-positive MCF-7 human breast carcinoma cell line and A549 human lung adenocarcinoma cell line, expressing a low level of FR. The results showed that MCF-7 cells internalize FA-functionalized nanoparticles to a greater extent than non-targeted ones and also than A549 cells. The competitive studies performed in the presence of FA in excess suggested that internalization is an FR-dependent process. The increased internalization of Fe₃O₄@PEG@FA@Curc nanoparticles in MCF-7 cells is correlated with increased cytotoxicity in this cell line compared to A549 cells. In conclusion, the FA-functionalized magnetic systems can ensure a better internalization of the nanoparticles and can be used to deliver various therapeutic agents, both in cancer treatment and also in the treatment of other inflammation-associated diseases such as rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, Crohn's disease or atherosclerosis.

Keywords: Cellular internalization; Folic acid decoration; Stabilized magnetite nanostructures; Targeted drug delivery; Tumor cells.