title: Novel dual stimuli-responsive ABC triblock copolymer: RAFT synthesis, "schizophrenic" micellization, and its performance as an anticancer drug delivery nanosystem.
abstract: A novel pH- and thermo-responsive ABC triblock copolymer {poly[(2-succinyloxyethyl methacrylate)-b-(N-isopropylacrylamide)-b-[(N-4-vinylbenzyl),N,N-diethylamine]]} [P(SEMA-b-NIPAAm-b-VEA)] was successfully synthesized via reversible addition of fragmentation chain transfer (RAFT) polymerization technique. The molecular weights of PHEMA, PNIPAAm, and PVEA segments in the synthesized triblock copolymer were calculated to be 10,670, 6140, and 9060gmol-1, respectively, from proton nuclear magnetic resonance (1H NMR) spectroscopy. The "schizophrenic" self-assembly behavior of the synthesized P(SEMA-b-NIPAAm-b-VEA) triblock copolymer under pH and thermal stimulus were investigated by means of1H NMR and ultraviolet-visible (UV-vis) spectroscopies as well as dynamic light scattering (DLS) and zeta potential (ξ) measurements. The doxorubicin hydrochloride (DOX)-loading capacity, and stimuli-responsive drug release ability of the synthesized triblock copolymer were also investigated. The biocompatibility of the synthesized triblock copolymer was confirmed through the assessing survival rate of breast cancer cell line (MCF7) using MTT assay. In contrast, DOX-loaded triblock copolymer exhibited an efficient anticancer performance in comparison with free DOX verified by MTT and DAPI staining assays. As the results, we envision that the synthesized P(SEMA-b-NIPAAm-b-VEA) triblock copolymer can be applied as an enhanced anticancer drug delivery nanosystem, mainly due to its smart physicochemical and biocompatibility properties.
authors.affiliation: Drug Applied Research Center, Tabriz University of Medical Sciences, P.O. Box: 51656-65811, Tabriz, Iran; Department of Medicinal Chemistry, Faculty of Pharmacy, Tabriz University of Medical Sciences, P.O. Box: 51664-14766, Tabriz, Iran.
authors.forename: Soodabeh
authors.initials: S
authors.lastname: Davaran
authors.affiliation: Department of Chemistry, Payame Noor University, P.O. Box: 19395-3697, Tehran, Iran.
authors.forename: Aliyeh
authors.initials: A
authors.lastname: Ghamkhari
authors.affiliation: Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, P.O. Box: 51548-53431, Tabriz, Iran.
authors.forename: Effat
authors.initials: E
authors.lastname: Alizadeh
authors.affiliation: Department of Chemistry, Payame Noor University, P.O. Box: 19395-3697, Tehran, Iran. Electronic address: b_massoumi@pnu.ac.ir.
authors.forename: Bakhshali
authors.initials: B
authors.lastname: Massoumi
authors.affiliation: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, P.O. Box: 51656-65811, Tabriz, Iran. Electronic address: m_jaymand@yahoo.com.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Jaymand
mesh_terms: D000178:Acrylamides / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology*; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000378:metabolism; D004339:Drug Compounding; D065546:Drug Liberation; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D061986:MCF-7 Cells; D008689:Methacrylates / Q000737:chemistry*; D008823:Micelles; D008970:Molecular Weight; D058105:Polymerization; D011137:Polystyrenes / Q000737:chemistry*; D013696:Temperature
chemical_list: D000178:Acrylamides; D000903:Antibiotics, Antineoplastic; D004337:Drug Carriers; D008689:Methacrylates; D008823:Micelles; D011137:Polystyrenes; D004317:Doxorubicin; C067295:N-isopropylacrylamide
keywords: Enhanced drug delivery; RAFT polymerization; Self-assembly; Stimuli-responsive; Triblock copolymer; “Schizophrenic”