Polyborane encapsulated liposomes prepared using pH gradient and reverse-phase evaporation for boron neutron capture therapy: biodistribution in tumor-bearing mice
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Various types of boron delivery for boron neutron capture therapy (BNCT) have been studied. To selectively destroy cancer cells, high accumulation and selective delivery of 10B into tumor tissue are required. In this study, we developed polyboranes from 1,2-dicarba-closo-dodecaborane as boron carriers, and they were encapsulated into liposomes using either the pH gradient or reverse phase evaporation. The encapsulation efficiency of the liposome prepared using the pH gradient was twice as high as that prepared using reverse-phase evaporation. These liposomes, with diameters of either 50 or 100 nm, were injected into the tail veins of tumor-bearing mice to evaluate their biodistribution at 4, 12, and 24 h post-administration. Boron concentration of the polyborane encapsulated liposomes prepared using the pH gradient achieved 110–150 μg/g of tumor tissue, and the liposomes prepared using the pH gradient were able to achieve an intratumoral 10B concentration of 20–30 μg/g without replacing 11B with 10B. Moreover, this liposome maintained a high 10B level in the tumor for at least 20 h. Average tumor/blood ratios of liposomes reached 5–15 at 4–24 h after injection. From these results, use of polyborane encapsulated liposomes prepared using the pH gradient for BNCT was suggested.
KeywordsBoron neutron capture therapy pH gradient Liposomes Drug delivery Dicarba-closo-dodecaborane Biodistribution: tumor-bearing mice
This work was supported by the MEXT-Supported Program for the Strategic Research Foundation at Private Universities, 2010-2014 (Grant Number S1001019).
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Conflict of interest
The authors declare that they have no conflicts of interest.
- 2.Maruyama K, Ishida O, Kasaoka S, Takizawa T, Utoguchi N, Shinohara A, 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. https://doi.org/10.1016/j.jconrel.2004.04.018 CrossRefPubMedGoogle Scholar
- 3.Vicente MGH, Wickramasinghe A, Nurco DJ, Wang HJH, Nawrocky MM, Makar M, Miura M (2003) Synthesis, toxicity and biodistribution of two 5,15-di[3,5-(nidocarboranylmethyl)phenyl]porphyrins in EMT-6 tumor bearing mice. Bioorganic Med Chem 11:3101–3108. https://doi.org/10.1016/S0968-0896(03)00240-2 CrossRefGoogle Scholar
- 4.Thirumamagal BTS, Zhao XB, Bandyopadhyaya AK, Narayanasamy S, Johnsamuel J, Tiwari R, Golightly DW, Patel V, Jehning BT, Backer MV, Barth RF, Lee RJ, Backer JM, Tjarks W (2006) Receptor-targeted liposomal delivery of boron-containing cholesterol mimics for boron neutron capture therapy (BNCT). Bioconjug Chem 17:1141–1150. https://doi.org/10.1021/bc060075d CrossRefPubMedGoogle Scholar
- 9.Yang W, Barth RF, Rotaru JH, Moeschberger ML, Joel DD, Nawrocky MM, Goodman JH (1997) Enhanced survival of glioma bearing rats following boron neutron capture therapy with blood-brain barrier disruption and intracarotid injection of boronophenylalanine. J Neuro-Oncol 33:59–70. https://doi.org/10.1023/A:1005769214899 CrossRefGoogle Scholar
- 10.Shirakawa M, Yamamto T, Nakai K, Aburai K, Kawatobi S, Tsurubuchi T, Yamamoto Y, Yokoyama Y, Okuno H, Matsumura A (2009) Synthesis and evaluation of a novel liposome containing BPA–peptide conjugate for BNCT. Appl Radiat Isot 67:S88–S90. https://doi.org/10.1016/j.apradiso.2009.03.101 CrossRefPubMedGoogle Scholar
- 12.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 1910–1991. doi: https://doi.org/10.1039/B406141A
- 13.Sudimack JJ, Adams D, Rotaru J, Shukla S, Yan J, Sekido M, Barth RF, Tjarks W, Lee RJ (2002) Folate receptor-mediated liposomal delivery of a lipophilic boron agent to tumor cells in vitro for neutron capture therapy. Pharm Res 19:1502–1508. https://doi.org/10.1023/A:1020408716807 CrossRefPubMedGoogle Scholar
- 19.Zheng Z, Jiang W, Zinn AA, Knobler CB, Hawthorne MF (1995) Facile electrophilic iodination of icosahedral carboranes. Synthesis of carborane derivatives with boron-carbon bonds via the palladium-catalyzed reaction of diiodocarboranes with grignard reagents. Inorg Chem 34:2095–2100. https://doi.org/10.1021/ic00112a023 CrossRefGoogle Scholar
- 22.Heber EM, Kueffer PJ, Lee MW Jr, Hawthorne MF, Garabalino MA, Molinari AJ, Nigg DW, Bauer W, Hughes AM, Pozzi ECC, Trivillin VA, Schwint AE (2012) Boron delivery with liposomes for boron neutron capture therapy (BNCT): biodistribution studies in an experimental model of oral cancer demonstrating therapeutic potential. Radiat Environ Biophys 51:195–204. https://doi.org/10.1007/s00411-011-0399-0
- 26.Harrigan PR, Wong KF, Redelmeier TE, Wheeler JJ, Cullis PR (1993) Accumulation of doxorubicin and other lipophilic amines into large unilamellar vesicles in response to transmembrane pH gradients. Biochim Biophys Acta 1149:329–338. https://doi.org/10.1016/0005-2736(93)90218-O CrossRefPubMedGoogle Scholar
- 32.Doi A, Kawabata S, Iida K, Yokoyama K, Kajimoto Y, Kuroiwa T, Shirakawa T, Kirihara M, Kasaoka S, Maruyama K, Kumada H, Sakurai Y, Masunaga SI, Ono K, Miyatake SI (2008) Tumor-specific targeting of sodium borocaptate (BSH) to malignant glioma by transferrin-PEG liposomes: a modality for boron neutron capture therapy. J Neuro-Oncol 87:287–294. https://doi.org/10.1007/s11060-008-9522-8 CrossRefGoogle Scholar