ABSTRACT The formation and physico-chemical properties of biomaterial, based on double-stranded (ds) DNA molecules and bearing high concentration of gadolinium, is described. This “rigid” biomaterial demonstrate a few unique properties: (i) the ds DNA molecules forming complexes with gadolinium are fixed in the spatial structure of “rigid” particles, (ii) an abnormal negative band in the circular dichroism spectrum permits to follow the formation of this biomaterial; (iii) local concentration gadolinium in the content of biomaterial can reach 40%. These properties show that we are dealing with a novel type of biomaterial strongly enriched by gadolinium. This opens a gateway for practical application of this
biomaterial for neutron-capture reactions. A first attempt to apply this material for neutron-capture reaction in combination with neutron generator of thermal neutron flux was performed. Positive result obtained at destruction of CHO cells allows one to state that the advantages of this biomaterial are a simple manipulation with it, a possibility to adjust its gadolinium content, long-term stability of its physico-chemical properties, as well as a reduced cost of neutron-capture experiment.
Cite this paper
nullY. Yevdokimov, V. Salyanov, S. Akulinichev, V. Skorkin, P. Spirin, N. Orlova, V. Popenko and V. Prassolov, "Novel Biomaterial for NCT - “Rigid” Particles of (DNA-gadolinium) Liquid-Crystalline Dispersions," Journal of Biomaterials and Nanobiotechnology, Vol. 2 No. 3, 2011, pp. 281-292. doi: 10.4236/jbnb.2011.23035.
 Yu. M., Yevdokimov, V. V Sythev, “Nanotechnology and nucleic acids”, Open Nanoscience Journal, Vol. 1, 2007, pp. 19-31.
 Yu. M. Yevdokimov, V. I. Salyanov, S. G. Skuridin, “From liquid crystals to DNA nanoconstructions”, Molecular Biology, Vol. 43, 2009, pp. 284-300.
 Yu. M. Yevdokimov, V. I. Salyanov, O. V. Kondrashina, V.I. Borshevsky, S. V. Semenov, A. A. Gasanov, I. V. Reshetov, V. D. Kuznetsov, V. N. Nikiforov, S. V. Akulinichev, M. V. Mordovskoi, S. I. Potashev, V. M. Skorkin, “Particles of liquid-crystalline dispersions formed by (nucleic acid–rare earth element) complexes as a potential platform for neutron capture therapy”, International Journal of Biological Macromolecules, Vol. 37, 2005, pp. 165-173.
 H. Tokumitsu, H. Ichikawa, T. K. Saha, Y. Fukumori, L. H. Block, “Design and preparation of gadolinium-loaded chitosan particles for cancer neutron capture therapy”, S.T.P. Pharma Sciences, Vol. 10, 2000, pp. 39-49.
 R. C. Greenwood, C. W. Reich, H. A. Baader, H. R. Koch, D. Breitig, O. W. B. Schult, B. Fogelberg, A. Backlin, W. Mampe, T. von Egidy, K. Schreckenbach, “Collective and two-quasiparticle states in 158Gd observed through study of radiation neutron capture in 157Gd”, Nuclear Physics, Vol. A 304, 1978, pp. 327-428.
 T. K Saha, K. Jono, H. Ichikawa, Y. Fukumori, “Preparation and evaluation of glutaraldehyde cross-linked chitosan microspheres as a gadolinium reservoir for neutron-capture therapy”, Chemical & Pharmaceutical Bulletin, Vol. 46, 1988, pp. 537-539.
 J. Greiberg, J. M. Wolf, J. Wyman, L. Zou, R. M. Terek, “Gadolinium inhibits thymidine incorporation and induces apoptosis in chondrocytes”, Journal of Orthopaedic Research, Vol. 19, 2001, pp. 797-801.
 J. P. Mizgerd, R. M. Molina, R. C. Stearns, J. D. Brain, A. E. Warner, “Gadolinium induces marcophage apoptosis”, Journal of Leukocyte Biology, Vol. 59, 1996, pp. 189- 195.
 Q. F. Leclercq, M. Cohen-Ohana, N. Mignet, A. Sharbati,. J. Herscovici, D. Sherman, G. Byk, “Design, synthesis, and evaluation of gadolinium cationic lipids as tools for biodistribution studies of gene delivery complexes”, Bioconjugate Chemistry, Vol. 14, 2003, pp. 119-119.
 H. Tokumitsu, J. Hiratsuka, Y. Sakurai, T. Kobayashi, H. Ichikawa, Y. Fukumori, “Gadolinium neutron-capture therapy using novel gadopentetic acid-chitosan complex nanoparticles: in vivo growth suppression of experimental melanoma solid tumor”, Cancer Letters, Vol. 150, pp. 177-182.
 H. Tokumitsu, H. Ichikawa, Y. Fukumori, “Chitosan-gadopentetic acid complex nanoparticles for gadolinium neutron-capture therapy of cancer: preparation of novel emulsion-droplet coalescence technique and characterization”, Pharmaceutical Research, Vol. 16, 1999, pp. 1830-1835.
 Yu. M. Yevdokimov, S. G Skuridin, G. B. Lortkipanidze, “Liquid-crystalline dispersions of nucleic acids”, Liquid Crystals, Vol. 12, 1992, pp. 1-16.
 V. N. Nikiforov, V. D. Kuznetsov, Yu. D. Nechipurenko, V. I. Salyanov, Yu. M. Yevdokimov, “Magnetic properties of copper as a constituent of nanobridges formed between spatially fixed deoxyribonucleic acid molecules”, JETP Letters, Vol. 81, 2005, pp. 327-329.
 D, De Soete, R. Gijbelts, J, Hoste, Neutron Activation Analysis, John Wiley and Sons, NY, 1972.
 S.V. Akulinichev, V. M. Skorkin, V. N. Nikiforov, V. I. Salyanov, A. I. Evseev, O.V. Kondrashina, Yu. M. Yevdokimov, “A new biomaterial based on the (DNA–Gd) complex: 1. Determination of gadolinium concentration in particles”, Med. Fizika, Vol.31, 2006, pp. 64-69.
 D. Keller, C. J. Bustamante, “Theory of the interaction of light with large inhomogeneous molecular aggregates.” Journal of Chemical Physics, Vol. 84, 1986, pp. 2972- 2979.
 M.-H. Kim, L. Ulibarri, D. Keller, C. Bustamante, “The psi-type dichroism of large molecular aggegates. III. Calculations”, Journal of Chemical Physics, Vol. 84, 1986, pp. 2981-2989.
 Y. Bouligand, “Cholesteric order in Biopolymers”, Polymer preprints (A.C.S.), Vol. 18, 1977, pp. 33-38.
 V. A. Belyakov, V. P Orlov, S. V Semenov, S. G Skuridin,. Yu. M. Yevdokimov, “Comparison of calculated and observed CD spectra of liquid crystalline dispersions formed from double-stranded DNA and from DNA complexes with coloured compounds”, Liquid Crystals, Vol. 20, 1996, pp. 777-784.
 F. D. Saeva, P. E. Sharpe, G. R Olin, “Сholesteric liquid crystal induced circular dichroism (LCID) V. Mechanic aspects of LCID”, Journal of the American Chemical Society, Vol. 95, 1973, pp. 7656-7659.
 H. Zipper, H. Brunner, J. Bernhagen, F. Vitzthum, “Investigation on DNA intercalation and surface binding by SYBR Green I, its structure determination and methdological implications”, Nucleic Acids Research, Vol. 32, 2004, pp. 3-10.
 T. Haertle, J. Augustyniak, W. Guschlbauer, “Is Tb3+ Fluorescence enhancement only due to binding to single stranded polynucleotides?”, Nucleic Acids Research, Vol. 9, 1981, pp. 6191-6197.
 F. E. Rosetto, E. Nieboer, “The interaction of metal ions with synthetic DNA: induction of conformational and structural transitions”, Journal of Inorganic Biochemistry, Vol. 54, 1994, pp. 167-186.
 V. I. Salyanov, A. I. Evseev, V. I. Popenko, A. A. Gasanov, K. A. Dembo, O. V. Kondrashina, E. V. Shtykova, Yu. M. Yevdokimov, “Gadolinium complexes of linear and liquid-crystalline DNA”. Biophysics, Vol. 52, 2007, pp. 288-292.
 D. Gersanovsky, P. Colson, C. Houssier, E. Fredericq, “Terbium (3+) as a probe of nucleic acid structure: Does it alter the DNA conformation in solution?”, Biochimica et Biophysica Acta, Vol. 35. 1985, pp. 313-325.
 D. S Gross., H. Simpkins, “Evidence for two-site binding in the terbium (III)-nucleic acid interaction”, The Journal of Biological Chemistry, Vol. 256, 1981, pp. 9593-9598.
 S. C. Ha, K. Lowenhaupt, A. Rich, Y. Kim, K. K. Kim, “Crystal structure of a junction between B-DNA and Z-DNA reveals two extruded bases”, Nature, Vol. 437, 2005, pp. 1183-1186.
 E. V. Shtykova, V. V. Volkov, V. I. Salyanov, Yu. M. Yevdokimov, “SAXS-data-based structural modeling of DNA–gadolinium complexes fixed in particles of cholesteric liquid-crystalline dispersions”, European Biophysics Journal, Vol. 39, 2010, pp. 1313-1322.
 Yu. M. Yevdokimov, S. G. Skuridin, Yu. D. Nechipurenko, M. A. Zakharov, V. I. Salyanov, A. A. Kurnosov, V. D. Kuznetsov, V. N. Nikiforov, “Nanoconstructions based on double-stranded nucleic acids”, International Journal of Biological Macromolecules, Vol. 36, 2005, pp. 103-115.
 D. Grasso, S. Fasone, C. La Rosa, V. Salyanov, “A calorimetric study of the different thermal behaviour of DNA in the isotropic and liquid-crystalline states”, Liquid. Crystals, Vol. 9, 1991, pp.299–305.
 D. Grasso, R. Gabriele-Campisi, “A DSC study of the liquid crystalline phases of salmon sperm DNA”, Liquid Crystals, Vol. 15, 1993, pp. 701-708.
 Yu. M. Yevdokimov, V. I. Salyanov, E. V. Shtykova, K. A. Dembo, V. V. V olkov, P. V. Spirin, A. S. Slusheva, V. S. Prassolov, “A transition in DNA molecule’s spatial ordering due to nano-scale structures changes”, The Open Nanoscience Journal, Vol. 2, 2008, pp. 17-28.
 Yu. M. Yevdokimov, “Liquid-crystalline forms of DNA and their biological function”, Liquid Crystals and their Practical Application, Vol. 3, 2003, pp. 10-47.
 Yu. M. Yevdokimov, V. I. Salyanov, K. A. Dembo, F. Spener, “Recognition of DNA molecules and their package in liquid crystals”, Sensory Systems, Vol. 13, 1999, pp. 158-169.
 L. Li, J. Yang, X. Wu, C. Sun, G. Zhou, ?Study on co-luminescence effect of terbium-gadolinium-nucleic acids-cetylpyridine bromide system“, Journal of Luminescence, Vol. 101, 2003, pp. 141-146.
 Yu. M. Yevdokimov, V. I. Salyanov, O. V. Kondrashina, A. A. Gasanov, E. V. Shtykova, K. A. Dembo, “Rare- earth-cation-induced change in the cholesteric twisting of neighboring nucleic acid molecules”. Journal of Experimental and Theoretical Physics, Vol. 104, 2007, pp. 499-507.
 P. A. Lessing, A. W. Erickson, “Synthesis and characterization of gadolinium phosphate neutron absorber”, Journal of the European Ceramic Society, Vol. 23, 2003, pp. 3049-3057.
 R. J. Mumper, M. Jay, “Formation and stability of lanthanide complexes and their encapsulation into polymeric microspheres”, The Journal of Physical Chemistry, Vol. 96, 1992, pp. 8626–8631.
 Y-H. Qi, Q.-Y. Zhang, L. Xu, “Correlation analysis of the structure and stability constants of gadolinium (III) complexes”, Journal of Chemical Information and Computer Sciences, Vol. 42, 2002, pp. 1471-1475.
 Y. Akine, N .Tokita, K. Tokuuye, M. Satoh, H. Churei, C. Le Pechoux, T. Kobayashi, K. Kanda, “Suppression of rabbit VX-2 subcutaneous tumor growth by gadolinium neutron capture therapy”, Japanese Journal of Cancer Research, Vol. 84, 1993, pp. 841-843.
 R. M. Brugger, J.-L. A. Shin, “Evaluation of gadolinium–157 as a neutron capture therapy agent”, Strahlentherapie und Onkologie, Vol. 165, 1989, pp. 153-156.
 R.F. Martin, G. D’Cunha, M. Pardee, B. J Allen, “Induction of double-strand breaks following neutron capture by DNA-bound 157Gd”, International Journal of Radiation Biology, Vol. 54, 1988, pp. 205-208.
 R.F. Martin, G. D’Cunha, M. Pardee, B. J Allen, “Induction of DNA double-strand breaks by 157Gd neutron capture”, Pigment cell research. Vol. 2, 1989, pp. 330-332.
 T. Goortley, R. Zamenhof, H. Nikjoo, “Calculated DNA damage from gadolinium Auger electron and relation to dose distribution in a head phantom”, International Journal of Radiation Biology. Vol. 80, 2004, pp. 933-940.
 S. V. Akulinichev, Yu. M. Yevdokimov, D. B. Labeznik, M. L. Plyaschkyavich, A. I. Evseev, V. I. Salyanov, B. M. Skorkin, “Biomaterial based on particles of the cholesteric liquid-crystalline dispersions of the (DNA-Gd) complexes. II. Secondary irradiation after neutron capture in particles”, Med. Fizika. Vol.32, 2006, pp. 54-58.
 J. T. Masiakowski, J. L. Horton, L. J. Peters, “Gadolinium neutron capture therapy fo brain tumors: a computer study”, Medical Physics, Vol. 19, 1992, pp. 1-8.
 T. Matsumoto, “Transport calculations of depth-dose distributions for gadolinium neutron capture therapy”, Physics in Medicine & Biology, Vol. 37, 1992, pp. 155- 162.