Bioengineering Functional Copolymers. XVII. Interaction of Organoboron Amide-Ester Branched Derivatives of Poly(Acrylic Acid) with Cancer Cells

Abstract

Novel bioengineering functional organoboron polymers were synthesized by 1) amidolysis of poly(acrcylic acid) (PAA) with 2-aminoethyldiphenyl borinate (2-AEPB), 2) esterification of organoboron PAA polymer (PAA-B) with a-hydroxy-methoxypoly(ethylene oxide) (PEO) as a compatibilizer and 3) conjugation of organoboron PEO branches (PAA-B-PEO) with folic acid (FA) as a targeting agent. Structure and composition of the synthesized polymers were characterized by FTIR-ATR and 1H (13C) NMR spectroscopy, chemical and physical analysis methods. Anti-tumor activity of organoboron functional polymer and its complex with FA (PAA-B-PEO-F) against cancer and normal cells were evaluated by using different biochemical methods such as cytotoxicity, statistical, apoptotic and necrotic cell indexes, double staining and caspase-3 immune staining, light and fluorescence inverted microscope analyses. It was found that citotoxicity and apoptotic/necrotic effects of polymers significantly depend on the structure and composition of studied polymers, and increase the following raw: PAA << PAA-B < PAA-B-PEO < PAA-B-PEO-F. Among them, PAA-B-PEO-F complex at 400 mg mL–1 concentration as a therapeutic drug exhibits minimal toxicity toward the nor-mal cells, but influential for HeLa cancer cells

Sytnhesis of Organoboron Amide-Ester Branched Derivatives of Poly(Itaconic Anhydride-alt-2-Vinyl-1,3-Dioxolane) and Cancer Cells Interaction Studies

“…When the organoboron copolymer containing PEO was incubated to cancer cells, the necrotic index decreased in cancer cells and normal cells (38% and 29%, respectively) ( Table 2 and 3). Similar results were reported at synthesized different boron compounds in previous studies [13,37,[46][47][48].…”

“…The cytotoxicity of PEO containing organoboron copolymer was lower than the one without PEO at 50-250 µg mL -1 concentrations. As it has shown in previous literature studies [13,37,[46][47][48] PEO was bound to organoboron copolymer, the cytotoxicity of organoboron amide-ester [Poly(IA-alt-VDO)-g-AEPB-g-PEO] derivative was decreased because of PEO biocompatibilization (it includes -OH end group and it has long chain structure) Also, the content of organoboron bond in boron containing copolymer was higher than organoboron amide-ester derivative. The poly(IA-alt-VDO) and its derivatives had a higher toxicity for cancer cells than normal cells.…”

“…The destruction process of supramacromolecular structure of cancer cell biomacromolecules could be influenced by the conjugation of copolymer with DNA biomacromolecules of cancer cell through cells/ionized amide and organoboron groups (-H 2 N...HOOC-) and H-bondings (O in ether...HOOC-) for this reason, can be exhibited apoptotic and necrotic effects [13,37,[46][47][48].…”

“…The number of viable cells was also around 80-65% for L929 Fibroblast cells and 50-30% for HeLa in the range of 100-200 µg mL -1 concentration. The cytotoxicity was increased because of organoboron linkage, hydrogen bonding, free carboxylic groups that are form of partial amidolysis of anhydride of pristine copolymer, whole hydrolysis of free anhydride units in the positive charged physiological condition [13,37,[46][47][48]. The cytotoxicity of PEO containing organoboron copolymer was lower than the one without PEO at 50-250 µg mL -1 concentrations.…”

“…Two types of the 10 B-compounds, sodium borocaptate (BSH) and l-4-dihydroxyboronylphenylalanine (BPA), have been used for clinical trials so far [54]. Many different types of bioactive boron-containing compounds have been investigated as therapeutic agents for BNCT [37,[46][47][53][54][55][56][57][58]. In our previous publications [37,[46][47], the design, synthesis, characterization and bioengineering properties of organoboron derivatives of various functional carboxyl/anhydride-containing copolymers, including alternating copolymer of MAH with VDO were reported.…”