title: Folic acid-conjugated polyethylene glycol-coated magnetic nanoparticles for doxorubicin delivery in cancer chemotherapy: Preparation, characterization and cytotoxicity on HeLa cell line.
abstract: Conventional chemotherapy is the most valid method to cope with cancer; however, it has serious drawbacks such as decrease in production of blood cells or inflammation of the lining of the digestive tract. These side effects occur since generally the drugs used in chemotherapy are distributed evenly within the body of the patient and cannot distinguish the cancer cells from the healthy ones. In this study, folic acid (FA)-conjugated, polyethylene-coated magnetic nanoparticles (FA-MNPs), and doxorubicin (Dox)-loaded formulation (Dox-FA-MNPs) were prepared. The cytotoxicity of these nanoparticles on HeLa and Dox-resistant HeLa cells was investigated. Magnetic nanoparticles (MNPs), polyethylene glycol (PEG)-coated MNPs (PEG-MNPs), and FA-MNPs were successfully synthesized and characterized by several methods. Dox loading of FA-MNPs and release profile of Dox from the nanoparticles were studied. Cytotoxic effects of FA-MNPs and Dox-FA-MNPs on HeLa cells were analyzed. MNPs, PEG-MNPs, and FA-MNPs all had small sizes and supermagnetic behavior. High amounts of Dox could be loded onto the nanoparticles (290 μgmL-1). In 24 h, 15.7% of Dox was released from the Dox-FA-MNPs. The release was increased in acidic conditions (pH 4.1). Internalization studies showed that FA-MNPs and Dox-FA-MNPs were taken up efficiently by HeLa cells. The investigation of cytotoxicity of the particles indicated that 38-500 μgmL-1Dox-FA-MNPs significantly decreased the proliferation of HeLa cells compared to FA-MNPs. Due to their size, magnetic properties, internalization, drug release, and cytotoxicity characteristics, the MNPs prepared in this study may have potential application as a drug delivery system in cancer chemotherapy.
authors.affiliation: 1 Department of Biology, Middle East Technical University, Ankara, Turkey.
authors.forename: M
authors.initials: M
authors.lastname: Erdem
authors.affiliation: 2 Department of Food Engineering, Ahi Evran University, Kirşehir, Turkey.
authors.forename: S
authors.initials: S
authors.lastname: Yalcin
authors.affiliation: 3 Department of Biotechnology, Middle East Technical University, Ankara, Turkey.
authors.forename: U
authors.initials: U
authors.lastname: Gunduz
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000494:pharmacology; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005492:Folic Acid / Q000737:chemistry / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D011092:Polyethylene Glycols; D004317:Doxorubicin; D005492:Folic Acid
keywords: Cancer; HeLa cell; cytotoxicity; magnetic nanoparticles