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

Codina Movileanu; Maria Anghelache; Mihaela Turtoi; Geanina Voicu; Ionela Andreea Neacsu; Denisa Ficai; Roxana Trusca; Ovidiu Oprea; Anton Ficai; Ecaterina Andronescu; Manuela Calin

doi:10.1016/j.ijpharm.2022.122064

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

Int J Pharm. 2022 Sep 25:625:122064. doi: 10.1016/j.ijpharm.2022.122064. Epub 2022 Aug 8.

Authors

Affiliations

¹ Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1-7 Gh Polizu Street, 011061 Bucharest, Romania; National Centre for Micro and Nanomaterials and National Centre for Food Safety, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Spl. Indendentei 313, 060042 Bucharest, Romania; Ilie Murgulescu" Institute of Physical Chemistry, Romanian Academy, 202 Spl. Independentei, 060021 Bucharest, Romania.
² "Medical and Pharmaceutical Bionanotechnologies" Laboratory, Institute of Cellular Biology and Pathology "Nicolae Simionescu" of the Romanian Academy, 050568 Bucharest, Romania.
³ Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1-7 Gh Polizu Street, 011061 Bucharest, Romania; National Centre for Micro and Nanomaterials and National Centre for Food Safety, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Spl. Indendentei 313, 060042 Bucharest, Romania; Academy of Romanian Scientists, 3 Ilfov Street, 050045 Bucharest, Romania.
⁴ National Centre for Micro and Nanomaterials and National Centre for Food Safety, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Spl. Indendentei 313, 060042 Bucharest, Romania; Department of Inorganic Chemistry, Physical Chemistry and Electrochemistry, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1-7 Gh Polizu Street, 050054 Bucharest, Romania.
⁵ National Centre for Micro and Nanomaterials and National Centre for Food Safety, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Spl. Indendentei 313, 060042 Bucharest, Romania.
⁶ Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, 1-7 Gh Polizu Street, 011061 Bucharest, Romania; National Centre for Micro and Nanomaterials and National Centre for Food Safety, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Spl. Indendentei 313, 060042 Bucharest, Romania; Academy of Romanian Scientists, 3 Ilfov Street, 050045 Bucharest, Romania. Electronic address: ecaterina.andronescu@upb.ro.

PMID: 35952802
DOI: 10.1016/j.ijpharm.2022.122064

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.

MeSH terms

Cell Line, Tumor
Curcumin* / pharmacology
Drug Carriers / chemistry
Drug Delivery Systems / methods
Folic Acid / chemistry
Humans
Magnetite Nanoparticles* / chemistry
Nanoparticles* / chemistry
Polyethylene Glycols / chemistry

Substances

Drug Carriers
Magnetite Nanoparticles
Polyethylene Glycols
Folic Acid
Curcumin