Bioengineering functional copolymers. XXI. Synthesis of a novel end carboxyl-trithiocarbonate functionalized poly(maleic anhydride) and its interaction with cancer cells

A novel carboxyl-trithiocarbonate functionalized polymer with a highly selective antitumor activity was synthesized by a reversible addition-fragmentation chain transfer (RAFT) polymerization of maleic anhydride (MA) with benzoyl peroxide as an initiator and S-1-dodecyl-S-(α,α′-dimethyl-α″-acetic acid)trithiocarbonate as a RAFT agent with the aim to design and synthesize an effective anticancer agent with minimum side effects. The structure, molecular weights and composition of synthesized polymers were investigated by 1H (13C) NMR, MALDI-TOF-MS and GPC analyzes. It was demonstrated that RAFT polymerization of MA was accompanied by a partially controlled decarboxylation of anhydride units and the formation of conjugated double bond fragments in backbone macromolecular chains. The mechanism of interaction of pristine RAFT agent and PMA–RAFT polymer with cancer (HeLa human cervix carcinoma) and normal (L929 Fibroblast) cells was investigated by using a combination of chemical, biochemical, statistical, spectroscopic (SEM and fluorescence inverted microscope) and real-time analysis (RTCA) methods. PMA–RAFT exhibited higher and selective cytotoxicity, apoptotic and necrotic effects toward HeLa cells at relatively low concentrations (around 7.5–75 μg mL−1, IC50 = 11.183 μg mL−1) and toward Fibroblast cells at high concentrations (IC50 >100 μg mL−1). The observed highly selective antitumor activity render PMA–RAFT polymers as promising candidates for the utilization in cancer chemotherapy.

Novel carboxyl-trithiocarbonate functionalized polymer with super selective antitumor activity synthesized by a RAFT controlled/living polymerization method. This multifunctional polymer surfactant with conjugated double bond in main chain used in the interactions with cancer and normal cells. The results of these investigations indicated that PMA–RAFT polymer exhibits higher cytotoxicity, apoptotic and necrotic effects against HeLa cells while it was non-cytotoxic toward Fibroblast cells in vitro. These results allow us recommend PMA–RAFT polymer for the cancer chemotherapy applications.Figure optionsDownload as PowerPoint slide