title: Design and construction of multifunctional hyperbranched polymers coated magnetite nanoparticles for both targeting magnetic resonance imaging and cancer therapy.
abstract: Magnetic drug targeting is a drug delivery strategy that can be used to improve the therapeutic efficiency on tumor cells and reduce the side effects on normal cells and tissues. The aim in this study is designing a novel multifunctional drug delivery system based on superparamagnetic nanoparticles for cancer therapy. Magnetic nanoparticles were synthesized by coprecipitation of iron oxide followed by coating with poly citric acid (PCA) dendritic macromolecules via bulk polymerization strategy. It was further surface-functionalized with poly(ethylene glycol) (PEG) and then to achieve tumor cell targeting property, folic acid was further incorporated to the surface of prepared carriers via a facile coupling reaction between the hydroxyl end group of the PEG and the carboxyl group of folic acid. The so prepared nanocarriers (Fe3O4@PCA-PEG-FA) were characterized by X-ray diffraction, TEM, TGA, FT-IR, DLS and VSM techniques. The room temperature VSM measurements showed that magnetic particles were superparamagnetic. Transmission electron microscopy and dynamic light scattering were also performed which revealed that size of nanocarriers was lying in the range of 10-49nm. Quercetin loading and release profiles of prepared nanocarriers showed that up to 83% of loaded drug was released in 250h. Fluorescent microscopy showed that the cellular uptake by folate receptor-overexpressing HeLa cells of the quercetin-loaded Fe3O4@PCA-PEG-FA nanoparticles was higher than that of non-folate conjugated nanoparticles. Thus, folate conjugation significantly increased nanoparticle cytotoxicity. Also, T2-weighted MRI images of Fe3O4@PCA-PEG-FA nanoparticles showed that the magnetic resonance signal is enhanced significantly with increasing nanoparticle concentration in water and they also served as MRI contrast agents with relaxivities of 3.4mM-1s-1(r1) and 99.8mM-1s-1(r2). The results indicate that this multifunctional nanocarrier is a significant breakthrough in developing a drug delivery vehicle that combines drug targeting as well as sensing and therapy at the same time.
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zanjan, P.O. Box 45195-313, Zanjan, Iran.
authors.forename: Asemeh
authors.initials: A
authors.lastname: Mashhadi Malekzadeh
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zanjan, P.O. Box 45195-313, Zanjan, Iran. Electronic address: aliramazani@gmail.com.
authors.forename: Ali
authors.initials: A
authors.lastname: Ramazani
authors.affiliation: Department of Chemistry, Faculty of Science, University of Zanjan, P.O. Box 45195-313, Zanjan, Iran. Electronic address: sjt.rezaei@znu.ac.ir.
authors.forename: Seyed Jamal
authors.initials: SJ
authors.lastname: Tabatabaei Rezaei
authors.affiliation: Department of Tissue Engineering, School of Advanced Technologies in Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran; Nanomedicine and Tissue Engineering Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hassan
authors.initials: H
authors.lastname: Niknejad
mesh_terms: D000975:Antioxidants / Q000008:administration & dosage; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D005492:Folic Acid / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000000981:diagnostic imaging* / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry*; D058105:Polymerization; D011794:Quercetin / Q000008:administration & dosage
chemical_list: D000975:Antioxidants; D004337:Drug Carriers; D058185:Magnetite Nanoparticles; D011092:Polyethylene Glycols; D005492:Folic Acid; D011794:Quercetin
keywords: Cancer chemotherapy; Magnetic nanoparticles; Magnetic resonance imaging; Targeted drug delivery