Bioengineering functional copolymers. XII. Interaction of boron-containing and PEO branched derivatives of poly(MA-alt-MVE) with HeLa cells
Mustafa Türk, Zakir M. O. Rzayev, Gülcihan Kurucu
DOI: 10.4236/health.2010.21009   PDF   HTML     4,248 Downloads   8,764 Views   Citations


Novel boron-containing bioengineering copoly- mer and its α-hydoxy-ω-methoxy-poly(ethy- lene oxide (PEO) macrobranched derivatives were synthesized by (1) partially amidolysis of poly(maleic anhydride-alt-methyl vinyl ether) w?th ethanolamine ester of diphenylboronic acid and (2) esterification of synthesized B-con- taining copolymers with PEO. They had a com- bination of hydrophilic/hydrophobic linkages, free carboxylic groups, positive charges and an ionized organoboron linkage as antitumor sites, along with an ability to interact with HeLa cells. The structure, composition and properties (cy- totoxicity and antitumor activity) of synthe- sized copolymers were investigated. In vitro cytotoxicity results, obtained by the fluore scence microscopy measurements indicate that unlike the virgin copolymer, boron-containing and PEO macrobranched derivatives exhibit higher antitumor activity. It was found that organoboron copolymer exhibits the most apo- ptotic and necrotic effects against HeLa cells whereas a minor effect relative to cancer cells was observed on L929 Fibroblast cells.

Share and Cite:

Türk, M. , Rzayev, Z. and Kurucu, G. (2010) Bioengineering functional copolymers. XII. Interaction of boron-containing and PEO branched derivatives of poly(MA-alt-MVE) with HeLa cells. Health, 2, 51-61. doi: 10.4236/health.2010.21009.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Albertsson, P.A. (1986) Partition of Cell Particles and Macromolecules. New York, Wiley.
[2] Herold, D.A., Keil, K., Bruns, D.E. (1989) Oxidation of polyethylene glycols by alcohol dehydrogenase.Biochem Pharmacol, 38(1), 73.
[3] Sinha, V.R., Aggarwal, A., Trehan, A. (2004) Biode- gradable PEGylated microspheres and nanospheres. Amer J Drug Deliv, 2(3), 157.
[4] K??eli, V., Rzaev, Z.M.O., Pi?kin, E. (2003) Bioengi- neering functional copolymers. III. Synthesis of biocom- patible poly(NIPA-co-MA)-g-PEO/PEI macrocomplexes and their thermostabilization effect on the activity of the enzyme penicillin G acylase. J Polym Sci Part A: Polym Chem, 41(11), 1580.
[5] Mazi, H., Kibarer, G., Emregül, E., Rzaev, Z.M.O. (2006) Bioengineering functional copolymers. IX. Poly[(maleic anhydride-co-hexene-1)-g-poly(ethylene oxide)]. Macro- mol Biosci, 6(4), 311.
[6] Mazi, H., Emregül, E., Rzaev, Z.M.O., Kibarer, G. (2006) Preparation and properties of invertase immobilized on a poly(maleic anhydride-hexen-1) membrane. J Biomater Sci, Polym Ed, 17, 821.
[7] Rzaev, Z.M.O., Din?er, S., Pi?kin, E. (2007) Functional copolymers of N-isopropyl-acrylamide for bioengineering applications. Prog Polym Sci, 32(5), 534.
[8] Butler, G.B. (1992) Cyclopolymerization and cyclopo- lymerization. New York, Marcel Dekker.
[9] Veron, L., Bignicount, M.C.D., Delair, T., Pichot, C., Mandrand, B. (1996) Syntheses of poly [N-(2,2-dimetho- xyethyl)-N-methyl acrylamide] for the immobilization of oligo-nucleotides. J Appl Polym Sci, 60(2), 235.
[10] Ladavière, C., Delair, T., Domard, A., Pichot, C., Man-drand, B. (1999) Covalent immobilization of biological molecules to maleic anhydride and methyl vinyl ether copolymers-A physico-chemical approach. J Appl Polym Sci, 71(6), 927.
[11] Chaix, C., Minard-Basquin, C., Delair, T., Pichot, C., and Mandrand, B. (1998) Oligonucleotide synthesis maleic anhydride copolymers covalently bound to silica spherical support and characterization of the on obtained conjugates. J Appl Polym Sci 70(12), 2487.
[12] Volkova, F., Gorshkova, M.Yu., Ivanov, P. E., Stotskaya, L. L. (2002) New scope for synthesis of divinyl ether and maleic anhydride copolymer with narrow molecular mass distribution. Polym Adv Technol, 13(10-12), 1067.
[13] Izumrudov, V.A., Gorshkova, M.Yu., Volkova, F. (2005) Controlled phase separations in solution of soluble poly-electrolyte complex of DIVEMA (copolymer of divinyl ether and maleic anhydride. Eur Polym J, 41(6), 1251.
[14] Ladavière, C., Delair, T., Domard, A., Pichot, C., Mandrand, B. (1999) Covalent immobilization of bovine serum albumin onto (maleic anhydride-alt-methyl vinyl ether) copolymers. J Appl Polym Sci, 72(12), 1565.
[15] Delair, T., Badey, B., Domard, A., Pichot, C., Mandrand, B. (1997) Polym Adv Technol, 8(5), 297.
[16] Patel, H., Raval, D.A., Madamwar, D., Sinha, T.J.M. (1997) Polymeric prodrugs. Synthesis, release study and antim-icrobial properties of polymer-bound acriflavine. Angew Makromol Chem, 245(1), 1.
[17] Patel, H., Raval, D.A., Madamwar, D., Patel, S.R. (1998) Polymeric prodrug: Synthesis, release study and anti- microbial property of poly(styrene-co-maleicanhy- dride)-bound acriflavine. Angew Makromol Chem, 263(1), 25.
[18] Hirano, T., Todorski, T., Kato, S., Yamamoto, H., Caliceti, P. (1994) Synthesis of the conjugate of superoxide dismutase with the copolymer of divinyl ether and maleic anhydride retaining enzymatic activity. J Control Release, 28(1-3), 203.
[19] Hirano, T., Todorski, T., Morita, R., Kato, S., Ito, Y., Kim, K., Shukla, G., Veronese, F., Maeda, H., Ohashi, S. (1997) Anti-inflammatory effect of the conjugate of superoxide dismutase with the copolymer of divinyl ether and maleic anhydride against rat re-expansion pulmonary edema. J Control Release, 48(2-3), 131.
[20] Maeda, H.H. (1991) SMANCS and polymer-conjugated macromolecular drugs: advantages in cancer chemo- therapy. Adv Drug Delivery Rev, 6(2), 181.
[21] Gam, G.-T., Jeong, J.-G., Lee, N.-J., Lee, W., Ha, C.-S., Cho, W.-J. (1995) Synthesis and biological activities of copolymers of N-glycinyl maleimide with methacrylic acid and vinyl acetate. J Appl Polym Sci, 57(2), 219.
[22] Claracq, J., Santos, S., Duhamel, J., Dumousseaux, C., Corpart, J.M. (2002) Rigid interior of styrene-maleic anhydride copolymer aggregates probes by fluorescence spectroscopy. Langmuir, 18(10), 3829.
[23] James, T.D., Sandanayake, S., Shinkay, S. (1996) Sac- charide sensing with molecular receptors based on boronic acid. Angew Chem Inter Ed Eng, 35(17), 1910.
[24] Barth, R.F., Yang, W., Rotaru, J.H., Moeschberger, M.L., Boesel, C.P., Soloway, A.H., Joel, D.D., Nawrocky, M.M., Ono, K., Goodman, J.H. (2000) Boron neutron cupture therapy of brain tumors: enchanced survival and cure following blood-brain barrier disruption and ?ntracarotid injection of sodium borocaptate and boronophenyl aniline. Int J Radiat Oncol Biol Phys, 47(1), 209.
[25] Siebert, W. (Ed.) (1887): Advances in Boron Chemistry. Cambridge, Royal Society Chemistry.
[26] Mishima Y. (Ed.) (1996) Cancer Neutron Capture Therapy. New York, Plenum Press.
[27] Kettner, C.A. and Shenvi, A.B. (1984) Inhibition of the serine proteases leukocyte elastase, pancreatic elastase, cathepsin G, and chymotrypsin by peptide boronic acids. J Biol Chem, 259(24), 15106. Miyazaki, H., Kikuchi, A., Kitano, S., Koyama, Y., Okano, T., Sakurai, Y., Kataoka, K. (1993)
[28] Boronate-containing polymer as novel mitogen for lymphocytes. Biochem Biophys Res Commun, 195(2), 829.
[29] Aoki, T., Nagao, Y., Terada, E., Sanui, K., Ogata N., Yamada, N., Sakurai, Y., Kataoka, K., Okano, T. (1995) Endothelial cell differentiation into capillary structures by copolymer surfaces with phenylboronic acid group. J Biomater Sci Polym Ed, 7(7), 539.
[30] Otsuka, H., Uchimura, E., Koshino, H., Okano, T., Kataoka, K. (2003) Anomalous binding profile of pheny-lboronic acid with N-acetylneuraminic acid (Neu5Ac) in aqueous solution with varying pH. J Am Chem Soc, 125(12), 3493.
[31] Uchimura, E., Otsuka, H., Okano, T., Sakurai, S., Kataoka, K. (2001) Totally synthetic polymer with lectin-like function: Induction of killer cells by the copolymer of 3-acryl-amidophenylboronic acid with N,N-dimethyla- crylamide. Biotech Bioeng, 72(3), 307.
[32] Otsuka,H., Ikeya, T., Okano, T., Kataoka, K. (2006) Activation of lymphocyte proliferation by boronate- containing polymer immobilised on substrate: The effect of boron content on lymphocyte proliferation. Eur Cells Mater, 12(1), 36.
[33] Kataoka, K., Miyazaki, N., Okano, T., Sakurai, Y. (1994) Sensitive glucose-induced change of the lower critical solution temperature of poly [N,N-dimethylacrylamide- co-3-(acrylamido) phenylboronic acid] in physiological saline. Macromolecules, 27(4), 1061.
[34] Uguzdo?an, E., Denkta?, E.B., Tuncel, A. (2002) RNA- sensitive N-isopropylacrylamide/vinylphenyl boronic acid random copolymer. Macromol Biosci, 2(5), 214.
[35] Uguzdo?an, E., Kayi, H., Denkta?, E.B., Patir, S., Tuncel, A. (2003) Stimuli-responsive properties of aminophen- ylboronic acid carrying thermosensitive copolymers. Po- lym Int, 52(5), 649.
[36] Shiomori, K., Ivanov, A.E., Galaev, I.Yu., Kawano, Y., Mattiasson, B. (2004) Thermo-responsive properties of sugar sensitive copolymer of N-isopropylacrylamide and 3-(acrylamido)phenylboronic acid Macromol Chem Phys, 205(1), 27.
[37] Rzayev, Z.M.O., Be?karde?, O. (2007) Boron-containing functional copolymers for bioengineering applications. Collect Czech Chem Commun, 72(12), 1591.
[38] Kahraman, G., Be?karde?, O., Rzayev, Z.M.O., Pi?kin, E. (2004) Bioengineering functional copolymers. VII. Synth- esis and characterization of boron-containing self-assem- bled supramolecular architectures. Polymer, 45(17), 5813.
[39] ?imen, E.K., Rzayev, Z.M.O., Pi?kin, E. (2005) Bioengi-neering functional copolymers. V. Synthesis LCST, and thermal behavior of poly(N-isopropylacry- lamide-co-p-vinyl-phenylboronic acid). J Appl Polym Sci, 95(3), 573.
[40] Rzayev, Z.M.O., Erdo?an, D., Türk, M., Pi?kin, E. (2008) Bioengineering functional copolymers. VIII. Stimuli-res- ponsive boron-containing graft copolymers and their poly(ethylene imine) macrocomplexes and DNA conju- gates. J Biol Chem, 36(2), 83.
[41] Türk, M., Dincer, S., Yulug, I.G., Piskin, E. (2004) In vitro transfection of HeLa cells with temperature sensitive polycationic copolymers. J Control Release, 96(2), 325.
[42] Choi, S.-J., Oh, J.-M., Choy, J.-H. (2009) Toxicological effects of inorganic nanoparticle nanoparticles on human lung cancer A549 cells. J Inorg Biochem, 103(3), 463.
[43] Ulukaya, E., Kurt, A., Wood, E.J. (2001) 4-(N-hydrox- yphenyl)retinamide can selectively induce apoptosis in human epidermoid carcinoma cells but not in normal dermal fibroblasts.Cancer Invest, 19(2), 145.
[44] McPartland, J.L., Guzail, M.A., Kendall, C.H., Pringle, J.H. (2005) Apoptosis in chronic viral hepatitis parallels histological activity: an immunohistochemical investi- gation using antiactivated caspase-3 and M30 cytodeath antibody. Int J Exp Pathol, 86(1), 19.

Copyright © 2021 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.