title: Cell uptake enhancement of folate targeted polymer coated magnetic nanoparticles.
abstract: Dual targeted drug delivery systems represent a potential platform for developing efficient vector to tumor sites. In this study we evaluated a folate- and magnetic-targeted nanocarriers based on 10 nm iron oxide nanodomais coated with the properly synthesized and characterized folic acid (FA)-functionalized amphiphilic copolymer PHEA-PLA-PEG-FA. FA was chemically conjugated to one end of diamino-polyethylene glycol of 2000 Da, in order to ensure its exposition on the polymer coated magnetic nanoparticles (MNPs-FA). The prepared nanoparticles have been exhaustively characterized by different methods, including DLS, SEM, FT-IR and magnetic measurements. Magnetic nanoparticles showed dimension of about 37 nm with a narrow size distribution and a characteristic superparamagnetic behaviour. The lack of cytotoxicity of MNPs-FA and MNPs was assessed both on MCF7 cells, used as a model tumor cell line, and on 16HBE, used as normal human cell model, by evaluating cell viability using MTS assay, while the preferential internalization of MNPs-FA into tumor cells rather that into normal cells was confirmed by the quantization of internalized iron oxide. Uptake studies were also performed in the presence of a permanent magnet in order to verify the synergistic effect of magnetic field in enhancing the internalization of magnetic nanoparticles. Finally, real-time confocal microscopy experiments were carried out to further confirmed that FA ligand enhances the MNPs-FA accumulation into cancer cell cytoplasm.
authors.affiliation: Department of Scienze e Tecnologie Molecolari e Biomolecolari, Laboratory of Biocompatible Polymers, University of Palermo, Via Archirafi, 32 90129 Palermo, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Licciardi
authors.forename: Cinzia
authors.initials: C
authors.lastname: Scialabba
authors.forename: Gennara
authors.initials: G
authors.lastname: Cavallaro
authors.forename: Claudio
authors.initials: C
authors.lastname: Sangregorio
authors.forename: Elvira
authors.initials: E
authors.lastname: Fantechi
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
mesh_terms: D045744:Cell Line, Tumor; D020099:Coated Materials, Biocompatible / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000627:therapeutic use; D005492:Folic Acid / Q000737:chemistry / Q000493:pharmacokinetics*; D006801:Humans; D061986:MCF-7 Cells; D058185:Magnetite Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry* / Q000648:ultrastructure; D008422:Materials Testing; D058990:Molecular Targeted Therapy / Q000379:methods*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D011108:Polymers / Q000737:chemistry*; D016896:Treatment Outcome
chemical_list: D020099:Coated Materials, Biocompatible; D058185:Magnetite Nanoparticles; D011108:Polymers; D005492:Folic Acid