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

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.