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Silica nanoparticles carrying boron-containing polymer brushes

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Abstract

A new class of surface-modified silica nanoparticles has been developed for potential applications in boron neutron capture therapy. Sub-50 nm silica particles were synthesized using a modified Stöber method and used in surface-initiated atom transfer radical polymerization of two biocompatible polymers, poly(2-(hydroxyethyl)methacrylate) and poly(2-(methacryloyloxy)ethyl succinate). The carboxylic acid and hydroxyl functionalities of the polymeric side chains were functionalized with carboranyl clusters in high yields. The resulting particles were characterized using DLS, TEM, solution 1H NMR, solid state 11B NMR and thermogravimetric analysis. The particles contain between 13 and 18 % of boron atoms by weight, which would provide a high amount of 10B nuclides for BNCT, while the polymer chains are suitable for further modification with cell targeting ligands.

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References

  • Barth RF, Adams DM, Soloway AH, Alam F, Darby MV (1994) Boronated starburst dendrimer-monoclonal antibody immunoconjugates: evaluation as a potential delivery system for neutron capture therapy. Bioconjugate Chem 5:58–66

    Article  Google Scholar 

  • Bregadze VI, Sivaev IB, Glazun SA (2006) Polyhedral boron compounds as potential diagnostic and therapeutic antitumor agents. Anti-Cancer Agents in Med Chem 6:75–109

    Article  Google Scholar 

  • Ceberg CP, Brun A, Kahl SB, Koo MS, Persson BR, Salford LG (1995) A comparative study on the pharmacokinetics and biodistribution of boronated porphyrin (BOPP) and sulfhydryl boron hydride (BSH) in the RG2 rat glioma model. J Neurosurg 83:86–92

    Article  Google Scholar 

  • Diaz A, Stelzer K, Laramore G, Wiersema R (2002) In: Sauerwein W, Moss R, Witting A (eds) Research and development in neutron capture therapy. Bologna, Monduzzi Editore, pp 993–994

    Google Scholar 

  • Feakes DA, Shelly K, Hawthorne MF (1995) Selective boron delivery to murine tumors by lipophilic species incorporated in the membranes of unilamellar liposomes. Proc Natl Acad Sci USA 92:1367–1370

    Article  Google Scholar 

  • Fréchet JMJ, Tomalia DA (2001) Dendrimers and other dendritic polymers. Wiley, New York

    Book  Google Scholar 

  • Friedlander G, Kennedy JW, Macias ES, Miller JM (1981) Nuclear and radiochemistry. Wiley, New York

    Google Scholar 

  • Galie KM, Mollard A, Zharov I (2006) Polyester-based carborane-containing dendrons. Inorg Chem 45:7815–7820

    Article  Google Scholar 

  • Gedda L, Olsson P, Ponten J, Carlsson J (1996) Development and in vitro studies of epidermal growth factor-dextran conjugates for boron neutron capture therapy. Bioconjug Chem 7:584–591

    Article  Google Scholar 

  • Gratton SEA, Parrott MC, Adronov A (2005) Preparation of carborane-containing polymers by atom transfer radical polymerization. J Inorg Organomet Polym 15:469–475

    Article  Google Scholar 

  • Hao E, Friso E, Miotto G, Jori G, Soncin M, Fabris C, Sabrian-Vazquez M, Vicente MGH (2008) Synthesis and biological investigations of tetrakis(p-carboranylthio-tetrafluorophenyl)chlorin (TPFC). Org Biolmol Chem 6:3732–3740

    Article  Google Scholar 

  • Hatanaka HA (1975) A revised boron-neutron capture therapy for malignant brain tumors. II. Interim clinical result with the patients excluding previous treatments. J Neurol 209:81–94

    Article  Google Scholar 

  • Hawthorne MF (1993) The role of chemistry in the development of cancer therapy by the boron-neutron capture reaction. Angew Chem Int Ed 32:950–984

    Article  Google Scholar 

  • Hoffman AS (2002) Hydrogels for biomedical applications. Adv Drug Delivery Rev 54:3–12

    Article  Google Scholar 

  • Isaac MF, Khal SB (2003) Synthesis of ether- and carbon-linked polycarboranyl porphyrin dimers for cancer therapies. J Organomet Chem 680:232–243

    Article  Google Scholar 

  • Jain P, Dai J, Baker GL, Bruening ML (2008) Rapid synthesis of functional polymer brushes by surface-initiated atom transfer radical polymerization of an acidic monomer. Macromolecules 41:8413–8417

    Article  Google Scholar 

  • Javid M, Brownell GL, Sweet WH (1952) The possible use of neutron-capturing isotopes such as boron10 in the treatment of neoplasms. II. Computation of the radiation energies and estimates of effects in normal and neoplastic brain. J Clin Invest 31:604–610

    Article  Google Scholar 

  • Kabalka GW, Yao ML (2003) Synthesis of a potential boron neutron capture therapy agent: 1-aminocyclobutane-1-carboxylic acid bearing a butylboronic acid side chain. Synthesis 18:2890–2893

    Article  Google Scholar 

  • Kato I, Ono K, Sakurai Y, Ohmae M, Maruhashi A, Imahori Y, Kirihata M, Nakazawa M, Yura Y (2004) Effectiveness of BNCT for recurrent head and neck malignancies. Appl Radiat Isot 61:1069–1073

    Article  Google Scholar 

  • Koivunoro H, Bleue DLl, Nastasi U, Lou TP, Reijonen J, Leung JN (2004) BNCT dose distribution in liver with epithermal D-D and D-T fusion-based neutron beams. Appl Radiat Isot 61:853–859

    Article  Google Scholar 

  • Kolonin MG, Pasqualini R, Arap W (2009) Tissue-specific targeting based on markers expressed outside endothelial cells. Adv Genetics 67:61–102

    Article  Google Scholar 

  • Kueffer PJ, Maitz CA, Khan AA, Schuster SA, Shlyakhtina NI, Jalisatgi SS, Brockman JD, Nigg DW, Hawthorne MF (2013) Boron neutron capture therapy demonstrated in mice bearing EMT6 tumors following selective delivery of boron by rationally designed liposomes. Proc Natl Acad Sci USA. doi:10.1073/pnas.1303437110

  • Lee JD, Ueno M, Miyajima Y, Nakamura H (2007) Synthesis of boron cluster lipids: closo-dodecaborate as an alternative hydrophilic function of boronated liposomes for neutron capture therapy. Org Lett 9:323–326

    Article  Google Scholar 

  • Li T, Hamdi J, Hawthorne MF (2006) Unilamellar liposomes with enhanced boron content. Bioconjug Chem 17:15–20

    Article  Google Scholar 

  • Malik N, Wiwattanapatapee R, Klopsch R, Lorenz K, Frey H, Weener JW, Meijer EW, Paulus W, Duncan R (2000) Dendrimers: relationship between structure and biocompatibility in vitro, and preliminary studies on the biodistribution of 125I-labeled polyamidoamine dendrimers in vivo. J Controlled Release 68:299–302

    Article  Google Scholar 

  • Maruyama K, Ishida O, Kasaoka S, Takizawa T, Utoguchi N, Shinohara M, Chiba M, Kobayashi H, Eriguchi M, Yanagie H (2004) Intracellular targeting of sodium mercaptoundecahydrododecaborate (BSH) to solid tumors by transferrin-PEG liposomes, for boron neutron-capture therapy (BNCT). J Control Release 98:195–207

    Article  Google Scholar 

  • Matyjaszewski K, Xia J (2001) Atom transfer tadical polymerization. Chem Rev 101:2921–2990

    Article  Google Scholar 

  • Meo CD, Panza L, Capitani D, Mannia L, Banzato A, Rondina M, Renier D, Rosato A, Crescenzi V (2007) Hyaluronan as carrier of carboranes for tumor targeting in boron neutron capture therapy. Biomacromolecules 8:552–559

    Article  Google Scholar 

  • Mishima Y, Honda C, Ichihasi M, Obara H, Hiratsuka J, Fukuda H, Karashima H, Kobayaki T, Kanda K, Yoshino K (1989) Treatment of malignant melanoma by single thermal neutron capture therapy with melanoma-seeking 10B-compound. Lancet 334:388–389

    Article  Google Scholar 

  • Miyajima Y, Nakamura H, Kuwata Y, Lee JD, Masunaga S, Ono K, Maruyama K (2006) Transferrin-loaded nido-carborane liposomes: tumor-targeting boron delivery system for neutron capture therapy. Bioconjug Chem 17:1314–1320

    Article  Google Scholar 

  • Mollard A, Zharov I (2006) Tricarboranyl pentaerythritol-based building block. Inorg Chem 45:10172–10179

    Article  Google Scholar 

  • Nakamura H, Miyajima Y, Takei T, Kasaoka S, Maruyama K (2004) Synthesis and vesicle formation of a nido-carborane cluster lipid for boron neutron capture therapy. Chem Commun 1910-1911

  • Nigg DW (2003) Computational dosimetry and treatment planning considerations for neutron capture therapy. J Neurooncol 62:75–86

    Google Scholar 

  • Nunez R, Gonzalex A, Vinas C, Teixidor F, Sillanpaa R, Kivekas R (2005) Approaches to the preparation of carborane-containing carbosilane compounds. Org Lett 7:231–233

    Article  Google Scholar 

  • Parrott MC, Marchington EB, Valliant JF, Adronov A (2005) Synthesis and properties of carborane-functionalized aliphatic polyester dendrimers. J Am Chem Soc 127:12081–12089

    Article  Google Scholar 

  • Qualmann B, Kessels MM, Musiol HJ, Sierralta WD, Jungblut PW, Moroder L (1996) Synthesis of boron-rich lysine dendrimers as protein labels in electron microscopy. Angew Chem Int Ed 35:909–911

    Article  Google Scholar 

  • Radin S, El-Bassyouni G, Vresilovic EJ, Schepers E, Ducheyne P (2005) In vivo tissue response to resorbable silica xerogels as controlled-release materials. Biomaterials 26:1043–1052

    Article  Google Scholar 

  • Rao M, Trivillin VA, Heber EM, Cantarelli ML, Itoiz ME, Nigg DW, Rebagliati RJ, Batistoni D, Schwint AE (2004) BNCT of 3 cases of spontaneous head and neck cancer in feline patients. Appl Radiat Isot 61:947–952

    Article  Google Scholar 

  • Shipp DA, Wang JL, Matyjaszewski K (1998) Synthesis of acrylate and methacrylate block copolymers using atom transfer radical polymerization. Macromolecules 31:8005–8008

    Article  Google Scholar 

  • Soloway AH, Tjarks W, Barnum BA, Rong FG, Barth RF, Codogni IM, Wilson JG (1998) The chemistry of neutron capture therapy. Chem Rev 98:1515–1562

    Article  Google Scholar 

  • Sumitani S, Nagasaki Y (2012) Boron neutron capture therapy assisted by boron-conjugated nanoparticles. Polymer J 44:522–530

    Article  Google Scholar 

  • Sweet WH, Javid M (1951) The possible use of slow neutrons plus boron-10 in therapy of intracranial tumors. Trans Am Neurol Assoc 76:60–63

    Google Scholar 

  • Thomas J, Hawthorne MF (2001) Dodeca(carboranyl)-substituted closomers: toward unimolecular nanoparticles as delivery vehicles for BNCT. Chem Commun 1884-1885

  • Tietze LF, Griesbach U, Bothe U, Nakamura H, Yamamoto Y (2002) Novel carboranes with a DNA binding unit for the treatment of cancer by boron neutron capture therapy. ChemBioChem 3:219–225

    Article  Google Scholar 

  • Tolpin EI, Wellum GR, Dophan FC, Kornblith PL, Zamenhof RG (1975) Boron neutron capture therapy of cerebral gliomas. II. Utilization of the blood-brain barrier and tumor-specific antigens for the selective concentration of boron in gliomas. Oncology 32:223–246

    Article  Google Scholar 

  • Ueno M, Ban HS, Nakai K, Inomata R, Kaneda Y, Matsumura A, Nakamura H (2010) Dodecaborate lipid liposomes as new vehicles for boron delivery system of neutron capture therapy. Bioorg Med Chem 18:3059–3065

    Article  Google Scholar 

  • Valliant JF, Guenther KJ, King AS, Morel R, Schaffer P, Sogbein OO, Stephson KA (2002) The medicinal chemistry of carboranes. Coord Chem Rev 232:173–230

    Article  Google Scholar 

  • van Blaaderen A, van Geest J, Vrij AJ (1992) Monodisperse colloidal silica spheres from tetraalkoxysilanes: particle formation and growth mechanism. Colloid Interface Sci 154:481–501

    Article  Google Scholar 

  • Woodhouse SL, Rendina LM (2001) Synthesis and DNA-binding properties of dinuclear platinum(II)-amine complexes of 1,7-dicarba-closo-dodecaborane(12). Chem Commun 23:2464–2465

    Google Scholar 

  • Wu G, Barth RF, Yang W, Chatterjee M, Tjarks W, Ciesielski MJ, Fenstermaker RA (2004) Site-specific conjugation of boron-containing dendrimers to anti-EGF receptor monoclonal antibody cetuximab (IMC-C225) and its evaluation as a potential delivery agent for neutron capture therapy. Bioconjug Chem 15:185–194

    Article  Google Scholar 

  • Yanagie H, Maruyama K, Takizawa T, Ishida O, Ogura K, Matsumoto T, Sakurai Y, Kobayashi T, Shinohara A, Rant J, Skvarc J, Ilic R, Kuhne G, Chiba M, Furuya Y, Sugiyama H, Hisa T, Ono K, Kobayashi H, Eriguchi M (2006) Application of boron-entrapped stealth liposomes to inhibition of growth of tumour cells in the in vivo boron neutron-capture therapy model. Biomed Pharmacother 60:43–50

    Article  Google Scholar 

  • Yang W, Wu G, Barth RF, Swindall MR, Bandyopadhyaya AK, Tjarks W, Tordoff K, Moeschberger M, Sferra TJ, Binns PJ, Riley KJ, Ciesielski MJ, Fenstermaker RA, Wikstrand CJ (2008) Molecular targeting and treatment of composite EGFR and EGFRvIII-positive gliomas using boronated monoclonal antibodies. Cancer Res 14:883–891

    Google Scholar 

  • Yao HJ, Grimes RN, Corsini M, Zanello P (2003) Polynuclear metallacarborane-hydrocarbon assemblies: metallacarborane dendrimers. Organometallics 22:4381–4383

    Article  Google Scholar 

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Acknowledgments

This work was supported by the University of Utah Research Foundation through a Seed Grant and by the National Science Foundation (DMR-1008251). We are grateful to James K. Harper (University of Utah) for recording solid state NMR spectra.

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  1. Department of Chemistry, University of Utah, 315 South 1400 East, Salt Lake City, UT, 84112, USA

    Eric M. Brozek, Alexis H. Mollard & Ilya Zharov

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  1. Eric M. Brozek
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  2. Alexis H. Mollard
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  3. Ilya Zharov
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Correspondence to Ilya Zharov.

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Brozek, E.M., Mollard, A.H. & Zharov, I. Silica nanoparticles carrying boron-containing polymer brushes. J Nanopart Res 16, 2407 (2014). https://doi.org/10.1007/s11051-014-2407-1

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