Biodistribution of Amine-Amide Chlorin e6 Derivative Conjugate with a Boron Nanoparticle for Boron Neutron-Capture Therapy
The aim of the investigation was to study the biodistribution of amino-amide chlorin e6 derivative conjugate with cobalt bis-dicarbollide as a potential boron transporter for the tasks of boron neutron-capture therapy.
Materials and Methods. The experiments were carried out on Balb/c mice with induced murine colon carcinoma CT-26. Amino-amide chlorin e6 derivative conjugate with cobalt bis-dicarbollide was administered intravenously, the dose being 5 and 10 mg/kg body mass. The sampling for microscopic study of the drug uptake in ex vivo organs and tissues was performed 3 h after the administration.
Results. Characteristic nanoconjugate fluorescent peak was found in most organs under study, significant selectivity of the compound being noticed. A high uptake level was recorded in the liver, spleen and lung tissue. At the dose of 5 mg/kg, the drug content in a tumor was not different from that in muscular tissue and skin; maximum uptake was found in the liver. If the dose was increased up to 10 mg/kg, the nanoconjugate content in a tumor appeared to be comparable with that in the liver, the tumor/muscle ratio of fluorescent signals was ~3.
Conclusion. The study showed the prospects for using photosensitizer conjugate (chlorin е6) with boron particles as a means to deliver boron into a tumor. The level of the preparation uptake in tumor tissue depends on a dose.
- Sivaev I.B., Bregadze V.I., Kuznetsov N.T. Derivatives of the closo-dodecaborate anion and their application in medicine. Russian Chemical Bulletin 2002; 51(8): 1362–1374, http://dx.doi.org/10.1023/A:1020942418765.
- Rozumenko V.D. Boron neutron capture therapy of brain tumors. Ukrainskiy neyrokhirurgicheskiy zhurnal 2001; 3: 4–12.
- Hartman T., Carlson J. Radiation dose heterogeneity in receptor and antigen mediated boron neutron capture therapy. Radiother Oncol 1994; 31(1): 61–75, http://dx.doi.org/10.1016/0167-8140(94)90414-6.
- Boron chemistry at the beginning of the 21st century. Bubnov Yu.N. (editor). Moscow: Editorial URSS; 2003; 376 p.
- Soloway A.H., Tjarks W., Barnum B.A., Rong F.G., Barth R.F., Codogni I.M., Wilson J.G. The chemistry of neutron-capture therapy. Chem Rev 1998; 98(4): 1515–1562, http://dx.doi.org/10.1021/cr941195u.
- Yokoyama K., Miyatake S., Kajimoto Y., Kawabata S., Doi A., Yoshida T., Asano T., Kirihata M., Ono K., Kuroiwa T. Pharmacokinetic study of BSH and BPA in simultaneous use for BNCT. J Neurooncol 2006; 78(3): 227–232, http://dx.doi.org/10.1007/s11060-005-9099-4.
- Goudgaon N.M., El-Kattan G.F., Schinazi R.F. Boron containing pyrimidines, nucleosides, and oligonucleotides for neutron capture therapy. Nucleosides and Nucleotides 1994; 13(1–3): 849–880, http://dx.doi.org/10.1080/15257779408013283.
- Neutron capture therapy — principles and application. Sauerwein W., Wittig A., Moss R., Nakagawa Y. (editors). Springer Science + Business Media; 2012, http://dx.doi.org/10.1007/978-3-642-31334-9.
- Yamamoto Y., Cai J., Nakamura H., Sadayori N., Asao N., Nemoto H. Synthesis of netropsin and distamycin analogues bearing o-carborane and their DNA recognition. Journal of Organic Chemistry 1995; 60(11): 3352–3357, http://dx.doi.org/10.1021/jo00116a018.
- Oenbrink G., Jurgenlimke P., Gabel D. Accumulation of porphyrins in cells influence of hydrophobicity aggregation and protein binding. Photochem Photobiol 1988; 48(4): 451–456, http://dx.doi.org/10.1111/j.1751-1097.1988.tb02844.x.
- Grin M.A., Titeev R.A., Brittal D.I., Chestnova A.V., Mironov A.F., Feofanov A.V., Lobanova I.A., Sivaev I.B., Bregadze V.I. Synthesis of cobalt bis(dicarbollide) conjugates with natural chlorins by the Sonogashira reaction. Russian Chemical Bulletin 2010; 59(1): 219–224, http://dx.doi.org/10.1007/s11172-010-0065-8.
- Efremenko A.V., Ignatova A.A., Grin M.A., Mironov A.F., Bregadze V.I., Sivaev I.B., Feofanov A.V. Confocal microscopy and spectral imaging technique: contribution to the development of neutron sensitizers for anticancer BNCT. In: Current microscopy contributions to advances in science and technology. A. Méndez-Vilas (editor). Spain: FORMATEX, 2012; p. 84–90.
- Ol'shevskaya V.A., Zaytsev A.V., Savchenko A.N., Shtil A.A., Cheong C.S., Kalinin V.N. Boronated porphyrins and chlorins as potential anticancer drugs. Bulletin of the Korean Chemical Society 2007; 28(11): 1910–1914.
- Efremenko A.V., Ignatova A.A., Grin M.A., Sivaev I.B., Mironov A.F., Bregadze V.I., Feofanov A.V. Chlorin e6 fused with a cobalt-bis(dicarbollide) nanoparticle provides efficient boron delivery and photoinduced cytotoxicity in cancer cells. Photochem Photobiol Sci 2014; 13(1): 92–102, http://dx.doi.org/10.1039/c3pp50226k.
- Grin M.A., Titeev R.A., Brittal D.I., Ulybina O.V., Tsiprovskiy A.G., Berzina M. Ya., Lobanova I.A., Sivaev I.B., Bregadze V.I., Mironov A.F. New conjugates of cobalt bis(dicarbollide) with chlorophyll a derivatives. Mendeleev Communications 2011; 21(2): 84–86, http://dx.doi.org/10.1016/j.mencom.2011.03.008.
- Freshni R.Ya. Kul’tura zhivotnykh kletok: prakticheskoe rukovodstvo [Culture of animal cells: practice guidelines]. Moscow: BINOM. Laboratoriya znaniy; 2010; 691 p.
- Kuznetsov S.S., Snopova L.B., Karabut М.М., Sirotkina М.А., Buyanova N.L., Kalganova Т.I., Elagin V.V., Senina-Volzhskaya I.V., Barbashova L.N., Shumilova A.V., Zagaynova E.V., Vitkin A., Gladkova N.D. Features of morphological changes in experimental ct-26 tumors growth. Sovremennye tehnologii v medicine 2015; 7(3): 32–39, http://dx.doi.org/10.17691/stm2015.7.3.04.
- Maeda H. Macromolecular therapeutics in cancer treatment: the EPR effect and beyond. Journal of Controlled Release 2012; 164(2): 138–144, http://dx.doi.org/10.1016/j.jconrel.2012.04.038.
- Juzeniene A. Chlorin e6-based photosensitizers for photodynamic therapy and photodiagnosis. Photodiagnosis Photodyn Ther 2009; 6(2): 94–96, http://dx.doi.org/10.1016/j.pdpdt.2009.06.001.
