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Colloid and Polymer Science

, Volume 295, Issue 9, pp 1455–1461 | Cite as

Detailed biodistribution of liposomes prepared with polyborane instead of cholesterol for BNCT: effects of PEGylation

  • Issei Takeuchi
  • Yukiko Ishizuka
  • Hiromi Uchiro
  • Kimiko Makino
Original Contribution

Abstract

Various drug delivery systems for boron neutron capture therapy (BNCT) have been developed. To selectively destroy cancer cells, the high accumulation and selective delivery of 10B into tumor tissue are required. In this study, a polyborane for BNCT with enhanced hydrophobicity was synthesized from decaborane as a boron carrier, and embedded into bare and PEGylated liposomes. These liposomes having diameters of 40–43 nm were injected into tail vein of tumor-bearing mice to evaluate their biodistribution. Boron concentrations in tumor and tumor/blood ratios of the liposomes were reached over 30 μg/g of tissue and over 5 at 8–24 h, respectively. At 12 h after injection, PEGylated liposomes were found in tumor with high boron level (130.0 μg/g of tissue). This result showed that the PEGylated liposomes with a diameter of 40 nm were able to achieve efficient intratumoral 10B amount without replacing the 11B with 10B.

Keywords

Boron neutron capture therapy PEGylation Liposomes Drug delivery Decaborane Biodistribution 

Notes

Acknowledgements

This work was supported by Program for Development of Strategic Research Center in Private Universities supported by MEXT (2010-2014).

Compliance with ethical standards

Mice were used in accordance with the Guidelines for Animal Experimentation of Tokyo University of Science, which are based on the Guidelines for Animal Experimentation of the Japanese Association for Laboratory Animal Science.

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Barth RF, Coderrea JA, Vicente MGH (2005) Boron neutron capture therapy of cancer: current status and future prospects. Clin Cancer Res 11:3987–4002. doi: 10.1158/1078-0432.CCR-05-0035 CrossRefGoogle Scholar
  2. 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. doi: 10.1016/j.jconrel.2004.04.018 CrossRefGoogle Scholar
  3. 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-(nido-carboranylmethyl)phenyl]porphyrins in EMT-6 tumor bearing mice. Bioorganic Med Chem 11:3101–3108. doi: 10.1016/S0968-0896(03)00240-2 CrossRefGoogle Scholar
  4. 4.
    Hawthorne MF, Shelly K (1997) Liposomes as drug delivery vehicles for boron agents. J Neuro-Oncol 33:53–58. doi: 10.1023/A:1005713113990 CrossRefGoogle Scholar
  5. 5.
    Allen TM, Hansen C (1991) Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim Biophys Acta 1068:133–141. doi: 10.1016/0005-2736(91)90201-I CrossRefGoogle Scholar
  6. 6.
    Lasic DD (1996) Doxorubicin in sterically stabilized liposomes. Nature 380:561–562. doi: 10.1038/380561a0 CrossRefGoogle Scholar
  7. 7.
    Maeda H, Wu J, Sawa T, Matsumura Y, Hori K (2000) Tumor vascular permeability and the EPR effect in macromolecular therapeutics: a review. J Cont Rel 65:271–284. doi: 10.1016/S0168-3659(99)00248-5 CrossRefGoogle Scholar
  8. 8.
    Shelly K, Feakes DA, Hawthorne MR, Schmidt PG, Krisch TA, Bauer WF (1992) Model studies directed toward the boron neutron-capture therapy of cancer: boron delivery to murine tumors with liposomes. Proc Natl Acad Sci 89:9039–9043. doi: 10.1073/pnas.89.19.9039 CrossRefGoogle Scholar
  9. 9.
    Feakes DA, Shelly K, Knobler CB, Hawthorne MF (1994) Na3[B20H17NH3]: synthesis and liposomal delivery to murine tumors. Proc Natl Acad Sci 91:3029–3033. doi: 10.1073/pnas.91.8.3029 CrossRefGoogle Scholar
  10. 10.
    Heber EM, Kueffer PJ, Lee Jr MW, 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. doi: 10.1007/s00411-011-0399-0 CrossRefGoogle Scholar
  11. 11.
    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 92:1367–1370. doi: 10.1073/pnas.92.5.1367 CrossRefGoogle Scholar
  12. 12.
    Takeuchi I, Tomoda K, Matsumoto K, Uchiro H, Makino K (2016) PEGylated liposomes prepared with polyborane instead of cholesterol for BNCT: characteristics and biodistribution evaluation. Colloid Polymer Sci 294:1679–1685. doi: 10.1007/s00396-016-3925-4 CrossRefGoogle Scholar
  13. 13.
    McKinley NF, O’Shea (2006) Carbolithiation of diphenylacetylene as a stereoselective route to (Z)-tamoxifen and related tetrasubstituted olefins. J Org Chem 71:9552–9555. doi: 10.1021/jo061949s CrossRefGoogle Scholar
  14. 14.
    Beer ML, Lemon J, Valliant JF (2010) Preparation and evaluation of carborane analogues of tamoxifen. J Med Chem 53:8012–8020. doi: 10.1021/jm100758j CrossRefGoogle Scholar
  15. 15.
    Li Y, Carroll PJ, Sneddon LG (2008) Ionic-liquid-promoted decaborane dehydrogenative alkyne-insertion reactions: a new route to o-carboranes. Inorg Chem 47:9193–9202. doi: 10.1021/ic800999y CrossRefGoogle Scholar
  16. 16.
    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. Bioorganic Med Chem 18:3059–3065. doi: 10.1016/j.bmc.2010.03.050 CrossRefGoogle Scholar
  17. 17.
    Hashizaki K, Itoh C, Sakai H, Yokoyama S, Taguchi H, Saito Y, Ogawa N, Abe M (1999) Effects of PEG chain length of phospholipid with covalently attached poly(ethylene glycol) (PEG) on the macroscopic state of liposomes. J Jpn Oil Chem Soc 48:871–876CrossRefGoogle Scholar
  18. 18.
    Kakihana H, Kotaka M, Satoh S, Nomura M, Okamoto M (1977) Fundamental studies on the ion-exchange separation of boron isotopes. Bull Chem Soc Jpn 50:158–163. doi: 10.1246/bcsj.50.158 CrossRefGoogle Scholar
  19. 19.
    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. doi: 10.1007/s11060-008-9522-8 CrossRefGoogle Scholar
  20. 20.
    Lukyanov AN, Elbayoumi TA, Chakilam AR, Torchilin VP (2004) Tumor-targeted liposomes: doxorubicin-loaded long-circulating liposomes modified with anti-cancer antibody. J Cont Rel 100:135–144. doi: 10.1016/j.jconrel.2004.08.007 CrossRefGoogle Scholar
  21. 21.
    Carlsson J, Kullberg EB, Capala J, Sjöberg S, Edwards K, Gedda L (2003) Ligand liposomes and boron neutron capture therapy. J Neuro-Oncol 62:47–59. doi: 10.1023/A:1023282818409 Google Scholar
  22. 22.
    Shmeeda H, Tzemach D, Mak L, Gabizon A (2009) Her2-targeted pegylated liposomal doxorubicin: retention of target-specific binding and cytotoxicity after in vivo passage. J Cont Rel 136:155–160. doi: 10.1016/j.jconrel.2009.02.002 CrossRefGoogle Scholar
  23. 23.
    Gabizon A, Shmeeda H, Horowitz AT, Zalipsky S (2004) Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid–PEG conjugates. Adv Drug Deliv Rev 56:1177–1192. doi: 10.1016/j.addr.2004.01.011 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Issei Takeuchi
    • 1
    • 2
    • 3
  • Yukiko Ishizuka
    • 1
  • Hiromi Uchiro
    • 1
    • 2
    • 3
  • Kimiko Makino
    • 1
    • 2
    • 3
  1. 1.Faculty of Pharmaceutical SciencesTokyo University of ScienceNodaJapan
  2. 2.Center for Drug Delivery ResearchTokyo University of ScienceNodaJapan
  3. 3.Center for Physical PharmaceuticsTokyo University of ScienceNodaJapan

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