Synthesis, characterization and cytotoxicity analyzes of novel AB-Type Amphiphilic Block Copolymers

Abstract

AB-type novel amphiphilic poly(L-lactide)-block-(N-isopropylacrylamide) (PLLA-b-PNIPAM) and poly(L-lactide)-block-(N-vinyl-pyrrolidone) (PLLA-b-PNVP), diblock copolymers were synthesized through the combined use of ring-opening polymerization (ROP) and controlled/living radical polymerization (CRP) techniques.  (PLLA-b-PNIPAM) block copolymer was prepared via combination of ROP and atom transfer radical polymerization (ATRP) using the novel PLLA-based ATRP macroinitiator. (PLLA-b-PNVP) block copolymer was synthesized via combination of ROP and reversible addition-fragmentation chain transfer (RAFT) polymerization using the PLLA-based RAFT macro chain transfer agent (CTA). For this purpose, at first 2,4-difluorobenzyl alcohol (1) was used to initiate the ROP of (L-LA) using tin(II) 2-ethylhexanoate Sn(Oct)₂ as a catalyst at 120 ℃ for synthesis of PLLA-OH (2). Secondly, bromoester end-functionalized PLLA-based ATRP macroinitiator (3) was synthesized by esterification of hydroxyl end group of (2). The first block copolymer, (PLLA-b-PNIPAM) (5), was synthesized by ATRP of NIPAM using (3) in presence of copper(I) chloride/tris[2-(dimethylamino)ethyl]amine (CuCl/Me₆TREN) as catalyst system in DMF/water at 25 °C. For the synthesis step of second block copolymer, at first PLLA macro chain transfer agent (CTA) (4) was then synthesized via substitution reaction of (3) with potassium ethyl xanthogenate (KEX) and finally PLLA-b-PNVP (6) diblock copolymer was prepared via RAFT polymerization of NVP using (4). The molecular structures of novel polymers (2-6) were elucidated by spectroscopic (FTIR and ¹H NMR) methods. In the application phase of this study, the effectiveness of copolymers was examined on cervical cancer cells. Cytotoxicity effects were evaluated in vitro on HeLa cell lines.