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Molecular Science of Fluctuations Toward Biological Functions pp 221–244Cite as

Membrane-Targeted Nanotherapy with Hybrid Liposomes for Cancer Cells Leading to Apoptosis

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Abstract

We have produced hybrid liposomes (HL) which can be prepared by sonication of a mixture of vesicular and micellar molecules in a buffer solution. The physical properties of HL such as size, shape, and membrane fluidity can be controlled by changing the constituents and compositional ratio. We have employed HL for chemotherapy and interesting results are as follows: (A) The uniform and stable structure of HL composed of L-α-dimyristoylphosphatidylcholine (DMPC) and polyoxyethylenedodecyl ether (C12(EO)n) with a diameter of 80 nm was revealed. (B) The remarkable inhibitory effects of HL on the growth of various tumor cells were attained in vitro. (C) Induction of apoptosis by HL was obtained and the pathway of apoptosis induced by HL was clarified. (D) A good correlation between the membrane fluidity of HL and inhibitory effects of HL for tumor cells was obtained. (E) Significantly chemotherapeutic effects were obtained using mice model of carcinoma after the treatment with HL without any side effects in vivo. (F) In clinical applications, prolonged survival and remarkable reduction of neoplasm were attained in patients with lymphoma after the treatment with HL without any side effects after the approval of the bioethics committee.

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References

  1. Allen TM, Hansen CJ, Martin F, Redemann C, Yan YA (1991) Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochem Biophys Acta 1066(1):29–36

    Article  CAS  Google Scholar 

  2. Dinney CPN, Utsugi T, Fidler IJ, von Eschenbach AC, Killion JJ (1992) Immunotherapy of murine renal adenocarcinoma by systemic administration of liposomes containing the synthetic macrophage activator cgp 31362 or cgp 19835a in combination with interleukin 2 or –interferon. Cancer Res 52(5):1155–1161

    CAS  Google Scholar 

  3. Diomede L, Colotta F, Piovani B, Re F, Modest EJ, Salmona M (1993) Induction of apoptosis in human leukemic cells by the ether lipid 1-octadecyl-2-methyl-rac-glycero-3-phosphocholine. A possible basis for its selective action. Int J Cancer 53(1):124–130

    Article  CAS  Google Scholar 

  4. Fendler JH (ed) (1982) Membrane mimetic chemistry. Wiley, New York

    Google Scholar 

  5. Fidler IJ, Lopez-Berestein G (eds) (1989) Liposomes in the therapy of infectious diseases and cancer. Alan R Liss, New York

    Google Scholar 

  6. Fujimoto K, Iwasaki C, Kawaguchi H, Yasugi E, Oshima M (1999) Cell membrane dynamics and the induction of apoptosis by lipid compounds. FEBS Lett 446(1):113–116

    Article  CAS  Google Scholar 

  7. Goto K, Matsumoto Y, Ueoka R (1995) Hybrid liposomes coupled to steric control with high enantioselectivity. J Org Chem 60(11):3342–3346

    Article  CAS  Google Scholar 

  8. Goto K, Tanaka Y, Matsumoto Y, Ueoka R (2008) Induction of apoptosis of human tumor cells by hybird liposomes including docosahexaenoic acid. Bioorg Med Chem Lett 18(6):1880–1883

    Article  CAS  Google Scholar 

  9. Ichihara H, Nagami H, Yamamoto K, Matsumoto Y, Ueoka R (2003) Chemotherapy with hybrid liposomes without any drug in vivo. Yakugaku Zasshi 123(1):25–34

    Article  CAS  Google Scholar 

  10. Ichihara H, Nagami H, Kiyokawa T, Matsumoto Y, Ueoka R (2008) Chemotherapy using hybrid liposomes along with induction of apoptosis. Anticancer Res 28(2):1187–1196

    CAS  Google Scholar 

  11. Ichihara H, Ueno J, Umebayashi M, Matsumoto Y, Ueoka R (2011) Chemotherapy with hybrid liposomes for acute lymphatic leukemia leading to apoptosis in vivo. Int J Pharm 406(1–2):173–178

    Article  CAS  Google Scholar 

  12. Imamura C, Kemura Y, Matsumoto Y, Ueoka R (1997) Remarkable inhibitory effects of hybrid liposomes on the growth of HL-60 cells coupled to induction of apoptosis. Biol Pharm Bull 20(10):1119–1121

    Article  CAS  Google Scholar 

  13. Ishiyama M, Shiga M, Sasamoto K, Mizoguchi M (1993) A new sulfonated tetrazolium salt that produces a highly water-soluble formazan dye. Chem Pharm Bull 41(6):1118–1122

    Article  CAS  Google Scholar 

  14. Iwamoto Y, Matsumoto Y, Ueoka R (2005) Induction of apoptosis of human lung carcinoma cells by hybrid liposomes containing polyoxyethylenedodecyl ether. Int J Pharm 292(1–2):231–239

    Article  CAS  Google Scholar 

  15. Kanno A, Kodama R, Terada Y, Matsumoto Y, Ueoka R (1998) Chemotherapy with hybrid liposomes for cancer: an experimental study. Drug Deliv Syst 13(1):101–105

    Article  CAS  Google Scholar 

  16. Kanno A, Terada Y, Tsuzaki Y, Matsumoto Y, Ueoka R (1999) Therapeutic effects of hybrid liposomes on mice model of lung carcinoma. Drug Deliv Syst 14(1):37–42

    Article  CAS  Google Scholar 

  17. Kanno A, Tsuzaki Y, Miyagi M, Matsumoto Y, Ueoka R (1999) Chemotherapy with hybrid liposomes for melanomatosis. Biol Pharm Bull 22(9):1013–1014

    Article  CAS  Google Scholar 

  18. Kitamura I, Kochi M, Matsumoto Y, Ueoka R, Kuratsu J, Ushio Y (1996) Intrathecal chemotherapy with 1,3-bis(2-chloroethyl)-1-nitorsourea encapsulated into hybrid liposomes for meningeal gliomatosis: an experimental study. Cancer Res 56(17):3986–3992

    CAS  Google Scholar 

  19. Klibanov AL, Maruyama K, Torchilin VP, Huang L (1990) Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett 268(1):235–237

    Article  CAS  Google Scholar 

  20. Komizu Y, Matsumoto Y, Ueoka R (2006) Membrane targeted chemotherapy with hybrid liposomes for colon tumor cells leading to apoptosis. Bioorg Med Chem Lett 16(23):6131–6134

    Article  CAS  Google Scholar 

  21. Komizu Y, Nakata S, Goto K, Matsumoto Y, Ueoka R (2011) Membrane-targeted nanotherapy with hybrid liposomes for tumor cells leading to apoptosis. ACS Med Chem Lett 2(4):275–279

    Article  CAS  Google Scholar 

  22. Komizu Y, Ueoka H, Ueoka R (2012) Selective accumulation and growth inhibition of hybrid liposomes to human hepatocellular carcinoma cells in relation to fluidity of plasma membranes. Biochem Biophys Res Commun 418(1):81–86

    Article  CAS  Google Scholar 

  23. Konno H, Suzuki H, Tadakuma T, Kumai K, Yasuda T, Kubota T, Ohta S, Nagaike K, Hosokawa S, Ishibiki K et al (1987) Antitumor effect of adriamycin entrapped in liposomes conjugated with anti-human alpha-fetoprotein monoclonal antibody. Cancer Res 47(16):4471–4477

    CAS  Google Scholar 

  24. Lasic DD (ed) (1993) Liposomes: from physics to applications. Elsevier Science Publishing Company, Amsterdam

    Google Scholar 

  25. Matsumoto Y, Ueoka R (1990) Studies on thermodynamics for hydrolysis. 3. Isokinetic temperature related to molecular location of reactants in coaggregates. J Org Chem 55(22):5797–5799

    Article  CAS  Google Scholar 

  26. Matsumoto Y, Yamada E, Hirano J, Oshige M, Iio M, Iwahara M, Ueoka R (1993) Specific inhibitory effect of hybrid liposomes on growth of human lymphoma human lymphocyte B hybridoma cells in vitro. Biol Pharm Bull 16(2):213–215

    Article  CAS  Google Scholar 

  27. Matsumoto Y, Imamura C, Ito T, Taniguchi C, Ueoka R (1995) Specific hybrid liposomes composed of phosphatidylcholine and polyoxyethylenealkyl ether with markedly enhanced inhibitory effect on the growth of tumor cells in vitro. Biol Pharm Bull 18(10):1456–1458

    Article  CAS  Google Scholar 

  28. Matsumoto Y, Kato T, Kemura Y, Tsuchiya M, Yamamoto M, Ueoka R (1999) Intracellular responses of hybrid liposomes against leukemia cells related to apoptosis with antitumor activity. Chem Lett 28(1):53–54

    Article  Google Scholar 

  29. Matsumoto Y, Kato T, Iseki S, Suzuki H, Nakano K, Iwahara M, Ueoka R (1999) Remarkably enhanced inhibitory effects of hybrid liposomes on the growth of specific tumor cells. Bioorg Med Chem Lett 9(14):1937–1940

    Article  CAS  Google Scholar 

  30. Matsumoto Y, Kato T, Suzuki H, Hirose S, Naiki Y, Hirashima M, Ueoka R (2000) Highly specific inhibitory effects of three-component hybrid liposomes including sugar surfactants on the growth of glioma cells. Bioorg Med Chem Lett 10(23):2617–2619

    Article  CAS  Google Scholar 

  31. Matsumoto Y, Iwamoto Y, Matsushita T, Ueoka R (2005) Novel mechanism of hybrid liposomes-induced apoptosis in human tumor cells. Int J Cancer 115(3):377–382

    Article  CAS  Google Scholar 

  32. Matsumoto Y, Tanaka Y, Goto K, Ueoka R (2008) Specific fixed aqueous layer of three-component hybrid liposomes related to inhibition of hepatoma cells growth. Chem Lett 37(1):118–119

    Article  CAS  Google Scholar 

  33. Matsuoka Y, Nagata M, Komizu Y, Ichihara H, Kawase S, Sawada Y, Matsumoto Y, Ueoka R (2008) Inhibitory effects of hybrid liposomes on the growth of gastric tumor cells established from cotton rats. Yakugaku Zasshi 128(10):1485–1492

    Article  CAS  Google Scholar 

  34. Nagami H, Yamamoto K, Ichihara H, Matsumoto Y, Ueoka R (2003) Induction of apoptosis by hybrid liposomes without antitumor drugs toward human breast tumor cells. J Chem Eng Jpn 36(9):1127–1129

    Article  CAS  Google Scholar 

  35. Nagami H, Nakano K, Ichihara H, Matsumoto Y, Ueoka R (2006) Two methylene groups in phospholipids distinguish between apoptosis and necrosis for tumor cells. Bioorg Med Chem Lett 16(4):782–785

    Article  CAS  Google Scholar 

  36. Nagami H, Matsumoto Y, Ueoka R (2006) Chemotherapy with hybrid liposomes for lymphoma without drugs in vivo. Int J Pharm 315(1–2):167–172

    Article  CAS  Google Scholar 

  37. Nakano K, Iwamoto Y, Takata W, Matsumoto Y, Ueoka R (2002) Specific accumulation and growth inhibitory effects of hybrid liposomes to hepatoma cells in vitro. Bioorg Med Chem Lett 12(22):3251–3254

    Article  CAS  Google Scholar 

  38. Negishi Y, Yoshizawa J, Yamazaki Y, Matsumoto Y, Ueoka R (2005) Inhibitory effect of drug-free hybrid liposomes on metastasis of mouse neuroblasoma. J Jpn Soc Pediatr Surg 41(7):930–937

    Google Scholar 

  39. Obeid LM, Knardic CM, Karolak LA, Hannun YA (1993) Programmed cell death induced by ceramide. Science 259(5102):1769–1771

    Article  CAS  Google Scholar 

  40. Ohta H, Yatomi Y, Seweeney EA, Hakomori S, Igarashi Y (1994) A possible role of sphingosine in induction of apoptosis by tumor necrosis factor-alpha in human neutrophils. FEBS Lett 355(3):267–270

    Article  CAS  Google Scholar 

  41. Papahadyopoulos D (ed) (1978) Liposomes and their uses in biology and medicine. New York Academy of Sciences, New York

    Google Scholar 

  42. Tanaka Y, Goto K, Matsumoto Y, Ueoka R (2008) Remarkably high inhibitory effects of docosahexaenoic acid incorporated into hybrid liposomes on the growth of tumor cells along with apoptosis. Int J Pharm 359(1–2):264–271

    Article  CAS  Google Scholar 

  43. Tanoue O, Baba M, Tokunaga Y, Goto K, Matsumoto Y, Ueoka R (1999) Steric-control for the enantioselective hydrolysis of amino acid esters with membrane-bound enzyme models. Tetrahedron Lett 40(11):2129–2132

    Article  CAS  Google Scholar 

  44. Tanoue O, Ichihara H, Goto K, Matsumoto Y, Ueoka R (2003) Steric-control for the enantioselective hydrolysis of amino acid esters in hybrid membrane systems. Chem Pharm Bull 51(2):224–226

    Article  CAS  Google Scholar 

  45. Ueoka R, Matsumoto Y (1984) Isokinetic discrimination of the reaction field for the enantioselective hydrolysis. -Hydrophobic interactions in the micellar and bilayer systems-. J Synth Org Chem Jpn 42(12):1088–1094

    Article  CAS  Google Scholar 

  46. Ueoka R, Moss RA, Swarup S, Matsumoto Y, Strauss G, Murakami Y (1985) Extraordinary micellar enantioselectivity coupled to altered aggregate structure. J Am Chem Soc 107(7):2185–2186

    Article  CAS  Google Scholar 

  47. Ueoka R, Matsumoto Y, Yoshino T, Hirose T, Kikuchi J, Murakami Y (1986) Enzyme-like enantioselective catalysis in the specific coaggregate system of vesicular and micellar surfactants. Chem Lett 15(1):127–130

    Article  Google Scholar 

  48. Ueoka R, Matsumoto Y, Yoshino T, Watanabe N, Omura K, Murakami Y (1986) Remarkable steric control for the enantioselective cleavage of amino acid esters. Chem Lett 15(10):1743–1746

    Article  Google Scholar 

  49. Ueoka R, Matsumoto Y, Yoshino T, Hirose T (1986) Enantioselective and diastereoselective cleavage of amino acid esters in coaggregates of controlled size. Tetrahedron Lett 27(10):1183–1186

    Article  CAS  Google Scholar 

  50. Ueoka R, Matsumoto Y, Moss AR, Swarup S, Sugii A, Harada K, Kikuchi J, Murakami Y (1988) Membrane matrix for the hydrolysis of amino acid esters with marked enantioselectivity. J Am Chem Soc 110(5):1588–1595

    Article  CAS  Google Scholar 

  51. Ueoka R, Matsumoto Y, Oyama H, Takekuma H, Iio M (1988) Effects of flavonoids in hybrid membranes on the activity of tripeptide as an enzyme model and their inhibition of hybridoma growth in vitro. Chem Pharm Bull 36(11):4640–4643

    Article  CAS  Google Scholar 

  52. Ueoka R, Dozono H, Matsumoto Y, Cho M, Kitahara K, Kato Y (1990) Steric control for the enantioselective hydrolysis of amino acid esters in coaggregates composed of phosphatidylcholine and Triton X-100. Chem Pharm Bull 38(1):219–220

    Article  CAS  Google Scholar 

  53. Ueoka R, Matsumoto Y, Dozono H, Yano Y, Hirasa H, Goto K, Kato Y (1990) Remarkable steric control for the enantioselective hydrolytic-cleavage of amino acid esters responding to ionic strength. Tetrahedron Lett 31(37):5335–5538

    Article  CAS  Google Scholar 

  54. Ueoka R, Yamada E, Yamashita O, Matsumoto Y, Kato Y (1991) Composition- and temperature-sensitive membranes composed of phosphatidylcholine and Triton X-100 for the remarkably enhanced stereoselective-hydrolysis. Tetrahedron Lett 32(45):6597–6600

    Article  CAS  Google Scholar 

  55. Ueoka R, Matsumoto Y, Kanno A, Tsuzaki K, Ichihara H (2000) Marked therapeutic effect of dimyristoylphosphatidylcholine liposomes on carcinoma mice model in vivo. Biol Pharm Bull 23(10):1262–1263

    Article  CAS  Google Scholar 

  56. Ueoka R, Matsumoto Y, Hirose S, Goto K, Goto M, Furusaki S (2002) Remarkably enhanced inhibitory effects of three-component hybrid liposomes including sugar surfactants on the growth of lung carcinoma cells. Chem Pharm Bull 50(4):563–565

    Article  CAS  Google Scholar 

  57. Ueoka R, Matsumoto Y, Goto K, Ichihara H, Komizu Y (2011) Membrane targeted chemotherapy with hybrid liposomes for tumor cells leading to apoptosis. Curr Pharm Des 17(17):1709–1719

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Applied Life Science, Graduate School of Engineering, Sojo University, 4-22-1 Ikeda, Kumamoto-shi, Kumamoto, 860-0082, Japan

    Ryuichi Ueoka, Yoko Matsumoto, Hideaki Ichihara & Yuji Komizu

Authors
  1. Ryuichi Ueoka
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  2. Yoko Matsumoto
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  3. Hideaki Ichihara
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  4. Yuji Komizu
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Correspondence to Ryuichi Ueoka .

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Editors and Affiliations

  1. Kyoto University, Kyoto, Japan

    Masahide Terazima

  2. Nara Institute of Science and Tech, Ikoma, Japan

    Mikio Kataoka

  3. Sojo University, Kumamoto, Japan

    Ryuichi Ueoka

  4. Nagoya University, Nagoya, Japan

    Yuko Okamoto

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Ueoka, R., Matsumoto, Y., Ichihara, H., Komizu, Y. (2016). Membrane-Targeted Nanotherapy with Hybrid Liposomes for Cancer Cells Leading to Apoptosis. In: Terazima, M., Kataoka, M., Ueoka, R., Okamoto, Y. (eds) Molecular Science of Fluctuations Toward Biological Functions . Springer, Tokyo. https://doi.org/10.1007/978-4-431-55840-8_11

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