title: Polymer grafted magnetic nanoparticles for delivery of anticancer drug at lower pH and elevated temperature.
abstract: Efficient and controlled delivery of therapeutics to tumor cells is one of the important issues in cancer therapy. In the present work, a series of pH- and temperature-responsive polymer grafted iron oxide nanoparticles were prepared by simple coupling of aminated iron oxide nanoparticle with poly(N-isopropylacrylamide-ran-poly(ethylene glycol) methyl ether acrylate)-block-poly(acrylic acid) (P(NIPA-r-PEGMEA)-b-PAA). For this, three water soluble block polymers were prepared via reversible addition fragmentation transfer (RAFT) polymerization technique. At first, three different block copolymers were prepared by polymerizing mixture of NIPA and PEGMEA (with varying mole ratio) in presence of poly(tert-butyl acrylate) (PtBA) macro chain transfer agent. Subsequently, P(NIPA-r-PEGMEA)-b-PAA copolymers were synthesized by hydrolyzing tert-butyl acrylate groups of the P(NIPA-r-PEGMEA)-b-PtBA copolymers. The resulting polymers were then grafted to iron oxide nanoparticles, and these functionalized nanoparticles were thoroughly characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), zeta potential measurements, transmission electron microscopy (TEM), field emission scanning electron microscopy (FESEM), vibrating sample magnetometer (VSM) and Fourier transform infrared spectroscopy (FTIR). Doxorubicin (DOX), an anti-cancer drug, was loaded into the polymer coated nanoparticles and its release behavior was subsequently studied at different pH and temperatures. The drug release pattern revealed a sustained release of DOX preferentially at the desired lysosomal pH of cancer cells (pH 5.0) and slightly above the physiological temperature depending upon the composition of the copolymers. The potential anticancer activity of the polymer grafted DOX loaded nanoparticles were established by MTT assay and apoptosis study of cervical cancer ME 180cells in presence of the nanoparticles. Thus, these particles can be utilized for controlled delivery of anticancer drugs at the desired lysosomal pH and/or by slightly heating the cells using magnetic hyperthermia.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Sujan
authors.initials: S
authors.lastname: Dutta
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Sheetal
authors.initials: S
authors.lastname: Parida
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Chiranjit
authors.initials: C
authors.lastname: Maiti
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Banerjee
authors.affiliation: School of Medical Science and Technology, Indian Institute of Technology Kharagpur, West Bengal 721302, India.
authors.forename: Mahitosh
authors.initials: M
authors.lastname: Mandal
authors.affiliation: Department of Chemistry, Indian Institute of Technology Kharagpur, West Bengal 721302, India. Electronic address: dibakar@chem.iitkgp.ernet.in.
authors.forename: Dibakar
authors.initials: D
authors.lastname: Dhara
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D015394:Molecular Structure; D010316:Particle Size; D011108:Polymers / Q000138:chemical synthesis / Q000737:chemistry*; D013499:Surface Properties; D013696:Temperature
chemical_list: D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D011108:Polymers
keywords: Apoptosis; Block copolymer; Doxorubicin; Iron oxide nanoparticles; Poly(N-isopropylacrylamide); Poly(ethylene glycol)