title: Specific targeting of cancer cells by multifunctional mitoxantrone-conjugated magnetic nanoparticles.
abstract: We report on the synthesis of bifunctional mitoxantrone (MTX)-grafted magnetic nanoparticles (MNPs) modified by dopamine-polyethylene glycol-folic acid (DPA-PEG-FA) for targeted imaging and therapy of cancer. MNPs (~7-10 nm) were synthesized using the thermal decomposition reaction of Fe(acac)3. Bromoacetyl (BrAc) terminal polyethylene glycol dopamine (DPA-PEG-BrAc) was synthesized and treated with ethylene diamine to form bifunctional PEG moiety containing dopamine at one end and amino group at the other end (i.e. DPA-PEG-NH2). It was then reacted with Fe3O4 nanoparticles (NPs) to form Fe3O4-DPA-PEG-NH2 NPs. The activated folic acid (FA) was chemically coupled to Fe3O4-DPA-PEG-NH2, forming Fe3O4-DPA-PEG-FA. MTX was then conjugated to Fe3O4-DPA-PEG-FA, forming Fe3O4-DPA-PEG-FA-MTX. Physicochemical characteristics of the engineered MNPs were determined. The particle size analysis and electron microscopy showed an average size of ~35 nm for Fe3O4-DPA-PEG-FA-MTX NPs with superparamagnetic behavior. FT-IR spectrophotometry analysis confirmed the conjugation of FA and MTX onto the MNPs. Fluorescence microscopy, cytotoxicity assay and flow cytometry analysis revealed that the engineered Fe3O4-DPA-PEG-FA-MTX NPs were able to specifically bind to and significantly inhibit the folate receptor (FR)-positive MCF-7 cells, but not the FR-negative A549 cells. Based upon these findings, we suggest the Fe3O4-DPA-PEG-FA-MTX NPs as an effective multifunctional-targeted nanomedicine toward simultaneous imaging and therapy of FR-positive cancers.
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Heidari Majd
authors.forename: Davoud
authors.initials: D
authors.lastname: Asgari
authors.forename: Jaleh
authors.initials: J
authors.lastname: Barar
authors.forename: Hadi
authors.initials: H
authors.lastname: Valizadeh
authors.forename: Vala
authors.initials: V
authors.lastname: Kafil
authors.forename: George
authors.initials: G
authors.lastname: Coukos
authors.forename: Yadollah
authors.initials: Y
authors.lastname: Omidi
mesh_terms: D045744:Cell Line, Tumor; D004298:Dopamine / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D005290:Ferric Compounds / Q000008:administration & dosage / Q000737:chemistry; D058972:Folic Acid Transporters / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008280:Magnetics / Q000379:methods*; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000737:chemistry* / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D010316:Particle Size; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D005290:Ferric Compounds; D058972:Folic Acid Transporters; C000499:ferric oxide; D011092:Polyethylene Glycols; D008942:Mitoxantrone; D004298:Dopamine