title: Tamoxifen loaded folic acid armed PEGylated magnetic nanoparticles for targeted imaging and therapy of cancer.
abstract: Magnetic nanoparticles (MNPs) have been widely used as drug delivery nanosystems and contrast agent for imaging and detection. To engineer multifunctional nanomedicines for simultaneous imaging and therapy of cancer cells, in the current study, we synthesized tamoxifen (TMX) loaded folic acid (FA) armed MNPs to target the folate receptor (FR) positive cancer cells. To this end, Fe3O4 nanoparticles (NPs) were synthesized through thermal decomposition of Fe(acac)3. Polyethylene glycol (PEG) was treated with excess bromoacetyl chloride (BrAc) and then with 3-aminopropyltriethoxysilane (APS) to synthesize bromoacetyl-terminal polyethylene glycol silane (APS-PEG-BrAc). The latter complex was treated with protected ethylene diamine to form a bifunctional PEG compound containing triethoxysilane at one end and amino group at the other end (APS-PEG-NH2). The Fe3O4-APS-PEG-NH2 NPs were prepared through self-assembly of APS-PEG-NH2 on MNPs, while the amino groups at the end of Fe3O4-APS-PEG-NH2 were conjugated with folic acid (FA), then loaded with TMX (Fe3O4-APS-PEG-FA-TMX). The average size of "Fe3O4-APS-PEG-FA-TMX" NPs was approximately 40 nm. The engineered MNPs were further characterized and examined in the human breast cancer MCF-7 cells that express FR. The TMX loaded MNPs (with loading efficiency of 49.1%) showed sustained liberation of TMX molecules (with 90% release in 72 h). Fluorescence microcopy and flow cytometry analyses revealed substantial interaction of Fe3O4-APS-PEG-FA-TMX NPs with the FR-positive MCF-7 cells. Cytotoxicity analysis resulted in significant growth inhibition in MCF-7 cells treated with Fe3O4-APS-PEG-FA-TMX NPs. Based on these findings, the TMX-loaded FA-armed PEGylated MNPs as a novel multifunctional nanomedicine/theranostic for concurrent targeting, imaging and therapy of the FR-positive cancer cells.
authors: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Mostafa
authors: M
authors: Heidari Majd
authors: Davoud
authors: D
authors: Asgari
authors: Jaleh
authors: J
authors: Barar
authors: Hadi
authors: H
authors: Valizadeh
authors: Vala
authors: V
authors: Kafil
authors: Alaleh
authors: A
authors: Abadpour
authors: Efat
authors: E
authors: Moumivand
authors: Javid Shahbazi
authors: JS
authors: Mojarrad
authors: Mohammad Reza
authors: MR
authors: Rashidi
authors: George
authors: G
authors: Coukos
authors: Yadollah
authors: Y
authors: Omidi
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D005492:Folic Acid / Q000008:administration & dosage* / Q000627:therapeutic use; D006801:Humans; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D011092:Polyethylene Glycols / Q000737:chemistry*; D013629:Tamoxifen / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D013629:Tamoxifen; D011092:Polyethylene Glycols; D005492:Folic Acid