Synthesis, Characterization and Cytotoxicity Analyzes of Novel ABA–Type PNIPAM-b-PLLA-b-PNIPAM Amphiphilic Block Copolymer

Abstract

Abstract: ABA–type amphiphilic poly(N-isopropylacrylamide)-block-poly(L-lactide)-block-poly(N-isopropylacrylamide) (PNIPAM-b-PLLA-b-PNIPAM) was synthesized via combination of ring opening polymerization (ROP) and atom transfer radical polymerization (ATRP) using the novel bifunctional PLLA–based ATRP macroinitiator bearing 1,2-bis[(3-oxapropyl)oxa]benzene core. For this purpose, at first bifunctional diol initiator, o-bis[(3-hydroxypropyl)oxy]benzene (1), was synthesized by the reaction of catechol and 3-chloro-1-propanol in the presence of sodium hydroxide (NaOH) in ethanol. Secondly, PLLA-diol (HO-PLLA-OH) was prepared by Sn(Oct)2 -catalyzed (ROP) of (L-LA) at 120°C using (1) as initiator in toluene. Thirdly, dibromoester end-functionalized PLLA-based ATRP macroinitiator (Br-PLLA-Br) was synthesized by esterification of hydroxyl end groups of PLLA-diol. Finally ABA-type block copolymer, (PNIPAM-b-PLLA-b-PNIPAM), was synthesized by (ATRP) of NIPAM as monomer using PLLA-based ATRP macroinitiator in presence of copper(I) chloride/tris[2-(dimethylamino)ethyl]amine (CuCl/Me6TREN) as catalyst system in DMF/water at 25°C. Characterization of the molecular structures for synthesized novel macroinitiator and the block copolymer were made by spectroscopic (FTIR and 1H NMR) and chromatographic (GPC) methods. In the application phase of this study, the effectiveness of polymers was examined on cancer cells. Cytotoxicity and metastatic effects were evaluated in vitro on MDA-MB-231 cell lines. As a result, novel ABA-Type PNIPAM-b-PLLA-b-PNIPAM amphiphilic block copolymer, which has been successfully developed, characterized and determined to be non-toxic, can be used as a promising drug delivery system in many areas such as tumor treatments.