Bioengineering functional copolymers. XIV. Synthesis and interaction of poly(N-isopropylacrylamide-co-3,4-dihydro-2H-pyran-alt-maleic anhydride)s with SCLC cancer cells

Abstract

Novel antitumor active functional polymers with supramacromolecular structures were synthesized by a complex-radical terpolymerization of N-isopropylacrylamide (NIPAm), 3,4-dihydro-2H-pyran (DHP), and maleic anhydride (MA) with 2,2'-azoisobisbutyronitrile as a radical initiator in 1,4-dioxane at 65 degrees C under nitrogen atmosphere. The structure and composition of terpolymers were investigated by H-1 (C-13) NMR spectroscopy. Interaction of terpolymers with human lung small cell carcinoma (SCLC) were investigated by using different methods such as cytotoxicity, statistical, apoptotic and necrotic cell indexes, double staining and caspase-3 immunostaining, light and fluorescence inverted microscopy analyses. Investigations into structure, composition, and antitumor activity relationships revealed that terpolymers containing a combination of ionisable amide-pyran linkages and H-bonded carboxylic groups exhibited higher cytotoxicity. It was observed that terpolymer with nearly alternating structure provides a maximum concentration of ionisable and H-bonded antitumor sites, and therefore, exhibits higher in vitro cytotoxicity, apoptotic and necrotic effects towards SCLC cancer cells. (C) 2010 Elsevier Ltd. All rights reserved.