Novel dual stimuli-responsive ABC triblock copolymer: RAFT synthesis, "schizophrenic" micellization, and its performance as an anticancer drug delivery nanosystem

Soodabeh Davaran; Aliyeh Ghamkhari; Effat Alizadeh; Bakhshali Massoumi; Mehdi Jaymand

doi:10.1016/j.jcis.2016.11.002

Novel dual stimuli-responsive ABC triblock copolymer: RAFT synthesis, "schizophrenic" micellization, and its performance as an anticancer drug delivery nanosystem

J Colloid Interface Sci. 2017 Feb 15:488:282-293. doi: 10.1016/j.jcis.2016.11.002. Epub 2016 Nov 2.

Authors

Soodabeh Davaran¹, Aliyeh Ghamkhari², Effat Alizadeh³, Bakhshali Massoumi⁴, Mehdi Jaymand⁵

Affiliations

¹ 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.
² Department of Chemistry, Payame Noor University, P.O. Box: 19395-3697, Tehran, Iran.
³ Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, P.O. Box: 51548-53431, Tabriz, Iran.
⁴ Department of Chemistry, Payame Noor University, P.O. Box: 19395-3697, Tehran, Iran. Electronic address: b_massoumi@pnu.ac.ir.
⁵ Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, P.O. Box: 51656-65811, Tabriz, Iran. Electronic address: m_jaymand@yahoo.com.

PMID: 27837719
DOI: 10.1016/j.jcis.2016.11.002

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 of ¹H 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.

Keywords: Enhanced drug delivery; RAFT polymerization; Self-assembly; Stimuli-responsive; Triblock copolymer; “Schizophrenic”.

MeSH terms

Acrylamides / chemistry*
Antibiotics, Antineoplastic / chemistry
Antibiotics, Antineoplastic / pharmacology*
Cell Survival / drug effects
Doxorubicin / chemistry
Doxorubicin / pharmacology*
Drug Carriers / chemical synthesis*
Drug Carriers / metabolism
Drug Compounding
Drug Liberation
Female
Humans
Hydrogen-Ion Concentration
Kinetics
MCF-7 Cells
Methacrylates / chemistry*
Micelles
Molecular Weight
Polymerization
Polystyrenes / chemistry*
Temperature

Substances

Acrylamides
Antibiotics, Antineoplastic
Drug Carriers
Methacrylates
Micelles
Polystyrenes
Doxorubicin
N-isopropylacrylamide