title: Magnetic core-shell hybrid nanoparticles for receptor targeted anti-cancer therapy and magnetic resonance imaging.
abstract: Hybrid nanoparticles with magnetic poly (lactide-co-glycolide) (PLGA) nanoparticle 'core', surface modified with folate-chitosan (fol-cht) conjugate 'shell' are evaluated as simultaneous anti-cancer therapeutic and MRI contrast agent. The fol-cht conjugate is prepared using carbodiimide crosslinking chemistry at an optimized folate to amine (chitosan) molar ratio for further coating on PLGA nanoparticles loaded with docetaxel and well packed super paramagnetic iron oxide nanoparticles (SPIONs). Apart from possessing a targeting moiety, the coating provides a physical barrier to avoid undesired burst release of drug and also imparts sensitivity to acidic pH, due to protonated amine group dependent decondensation of the coating and subsequent drug release. The biocompatible hybrid nanoparticles provide receptor targeted docetaxel and SPION delivery for anti-cancer therapy and magnetic resonance (MR) imaging respectively, as tested in both folate receptor positive and negative cancer cells. Enhancement in nanoparticle uptake by folate receptor positive oral cancer cells caused significant increase in docetaxel mediated cytotoxicity. While polymeric encapsulation and fol-cht coating negatively affects the magnetic property of iron oxide nanoparticles, their aggregation in the core, shortened the overall T2relaxation time thereby enhancing the nanoparticle relaxivity to provide better in vitro MR imaging.
authors.affiliation: Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India; Institute of Nano Science and Technology, Sector-64, Phase-10, Mohali 160062, India.
authors.forename: Asifkhan
authors.initials: A
authors.lastname: Shanavas
authors.affiliation: Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India.
authors.forename: Sisini
authors.initials: S
authors.lastname: Sasidharan
authors.affiliation: Department of Metallurgical Engineering and Materials Science, IIT Bombay, Powai, Mumbai 400076, India. Electronic address: dhirenb@iitb.ac.in.
authors.forename: Dhirendra
authors.initials: D
authors.lastname: Bahadur
authors.affiliation: Department of Biosciences and Bioengineering, IIT Bombay, Powai, Mumbai 400076, India. Electronic address: rsrivasta@iitb.ac.in.
authors.forename: Rohit
authors.initials: R
authors.lastname: Srivastava
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002234:Carbodiimides / Q000737:chemistry; D045744:Cell Line, Tumor; D048271:Chitosan / Q000737:chemistry; D003287:Contrast Media / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry; D000077143:Docetaxel; D004339:Drug Compounding; D065546:Drug Liberation; D004847:Epithelial Cells / Q000187:drug effects* / Q000473:pathology / Q000648:ultrastructure; D005290:Ferric Compounds / Q000737:chemistry*; D058975:Folate Receptor 1 / Q000235:genetics / Q000378:metabolism; D005492:Folic Acid / Q000737:chemistry; D015870:Gene Expression; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry* / Q000378:metabolism; D008279:Magnetic Resonance Imaging / Q000379:methods; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D011100:Polyglycolic Acid / Q000737:chemistry* / Q000378:metabolism; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D043823:Taxoids / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D002234:Carbodiimides; D003287:Contrast Media; D003432:Cross-Linking Reagents; D005290:Ferric Compounds; D058975:Folate Receptor 1; D058185:Magnetite Nanoparticles; D043823:Taxoids; D000077143:Docetaxel; C000499:ferric oxide; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D048271:Chitosan; D005492:Folic Acid
keywords: Core-shell; Folate-chitosan; MRI; Magnetic PLGA; Receptor targeting