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Peptide Characterization and Application Protocols pp 269–298Cite as

Peptide-Mediated Targeting of Liposomes to Tumor Cells

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Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 386))

Summary

One of the biggest obstacles for efficient drug delivery is specific cellular targeting. Liposomes have long been used for drug delivery, but do not possess targeting capabilities. This limitation may be circumvented by surface coating of colloidal delivery systems with peptides, proteins, carbohydrates, vitamins, or antibodies that target cell surface receptors or other biomolecules. Each of these coatings has significant drawbacks. One idealized system for drug delivery combines stabilized “protein module” ligands with a colloidal delivery vehicle. Prior studies have shown that peptide-amphiphiles, whereby both a peptide “head group” and a lipid-like “tail” are present in the same molecule, can be used to engineer collagen-like triple-helical or α-helical miniproteins. The tails serve to stabilize the head group structural elements. These peptide-amphiphiles can be designed to bind to specific cell surface receptors with high affinity. Structural stabilization of the integrated targeting ligand in the peptide-amphiphile system equates to prolonged in vivo stability through resistance to proteolytic degradation. Liposomes have been prepared incorporating a melanoma targeting peptide-amphiphile ligand, and shown to be stable with retention of peptide-amphiphile triple-helical structure. Encapsulated fluorescent dyes are selectively delivered to cells. In this chapter we describe the methods and techniques employed in the preparation and characterization of peptide-amphiphiles and peptide-amphiphile-targeted large and small unilamellar vesicles (LUVs and SUVs). Fluorescence microscopy is subsequently utilized to examine the targeting capabilities of peptide-amphiphile LUVs, which should allow for improved drug selectivity towards melanoma vs normal cells based on differences in the relative abundance of the targeted cell surface receptors.

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References

  1. Guo, X. and Szoka, F. C., Jr. (2003) Chemical approaches to triggerable lipid vesicles for drug and gene delivery. Acc. Chem. Res. 36, 335–341.

    Article  PubMed  CAS  Google Scholar 

  2. Allen, T. M. and Cullis, P. R. (2004) Drug delivery systems: entering the mainstream. Science 303, 1818–1822.

    Article  PubMed  CAS  Google Scholar 

  3. Martini, A. and Ciocca, C. (2003) Drug delivery systems for cancer drugs. Expert Opin. Ther. Patents 13, 1801–1807.

    Article  CAS  Google Scholar 

  4. Lasic, D. D. (1993) Liposomes: From Physics to Applications. Elsevier, Amsterdam.

    Google Scholar 

  5. Klibanov, A. L., Maruyama, K., Torchilin, V. P., and Huang, L. (1990) Amphipathic polyethyleneglycols effectively prolong the circulation time of liposomes. FEBS Lett. 268, 235–237.

    Article  PubMed  CAS  Google Scholar 

  6. Allen, T. M., Hansen, C., Martin, F., Redemann, C., and Yau-Young, A. (1991) Liposomes containing synthetic lipid derivatives of poly(ethylene glycol) show prolonged circulation half-lives in vivo. Biochim. Biophys. Acta 1066, 29–36.

    Article  PubMed  CAS  Google Scholar 

  7. Allen, T. M. and Hansen, C. (1991) Pharmacokinetics of stealth versus conventional liposomes: effect of dose. Biochim. Biophys. Acta 1068, 133–141.

    Article  PubMed  CAS  Google Scholar 

  8. Maruyama, K., Ishida, O., Takizawa, T., and Moribe, K. (1999) Possibility of active targeting to tumor tissues with liposomes. Adv. Drug Deliv. Rev. 40, 89–102.

    Article  PubMed  CAS  Google Scholar 

  9. Oku, N. (1999) Anticancer therapy using glucuronate modified long-circulating liposomes. Adv. Drug Deliv. Rev. 40, 63–73.

    Article  PubMed  CAS  Google Scholar 

  10. Gabizon, A. A. (2001) Pegylated liposomal doxorubicin: metamorphosis of an old drug into a new form of chemotherapy. Cancer Invest. 19, 424–436.

    Article  PubMed  CAS  Google Scholar 

  11. Jamil, J., Sheikh, S., and Ahmad, I. (2004) Liposomes: the next generation. Mod. Drug Discovery 7(1), 36–39.

    CAS  Google Scholar 

  12. Foldvari, M., Mezei, C., and Mezei, M. (1991) Intracellular delivery of drugs by liposomes containing Po glycoprotein from peripheral nerve myelin into human M21 melanoma cells. J. Pharm. Sci. 80, 1020–1028.

    Article  PubMed  CAS  Google Scholar 

  13. Hallahan, D., Geng, L., Qu, S., et al. (2003) Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels. Cancer Cell 3, 63–74.

    Article  PubMed  CAS  Google Scholar 

  14. Jaafari, M. R. and Foldvari, M. (2002) Targeting of liposomes to melanoma cells with high levels of ICAM-1 expression through adhesive peptides from immunoglobulin domains. J. Pharm. Sci. 91, 396–404.

    Article  PubMed  CAS  Google Scholar 

  15. Medina, O. P., Söderlund, T., Laakkonen, L. J., Tuominen, E. K. J., Koivunen, E., and Kinnunen, P. K. J. (2001) Binding of novel peptide inhibitors of type IV collagenases to phospholipid membranes and use in liposome targeting to tumor cells in vitro. Cancer Res. 61, 3978–3985.

    PubMed  CAS  Google Scholar 

  16. Eliaz, R. E. and Szoka, J., F.C. (2001) Liposome-encapsulated doxorubicin targeted to CD44: a strategy to kill CD44-overexpressing tumor cells. Cancer Res. 61, 2592–2601.

    PubMed  CAS  Google Scholar 

  17. Eliaz, R. E., Nir, S., Marty, C., and Szoka, F., Jr. (2004) Determination and modeling of kinetics of cancer cell killing by doxorubicin and doxorubicin encapsulated in targeted liposomes. Cancer Res. 64, 711–718.

    Article  PubMed  CAS  Google Scholar 

  18. Goren, D., Horowitz, A. T., Tzemach, D., Tarshish, M., Zalipsky, S., and Gabizon, A. (2000) Nuclear delivery of doxorubicin via folate-targeted liposomes with bypass of multidrug-resistance efflux pump. Clin. Cancer Res. 6, 1949–1957.

    PubMed  CAS  Google Scholar 

  19. Kirpotin, D., Park, J. W., Hong, K., et al. (1997) Sterically stabilized anti-HER2 immunoliposomes: design and targeting to human breast cancer cells in vitro. Biochemistry 36, 66–75.

    Article  PubMed  CAS  Google Scholar 

  20. Lee, C. M., Tanaka, T., Murai, T., et al. (2002) Novel chondroitin sulfate-binding cationic liposomes loaded with cisplatin effectively suppress the local growth and liver metastasis of tumor cells in vivo. Cancer Res. 62, 4282–4288.

    PubMed  CAS  Google Scholar 

  21. Schmitt-Sody, M., Strieth, S., Krasnici, S., et al. (2003) Neovascular targeting therapy: Paclitaxel encapsulated in cationic liposomes improves antitumoral efficacy. Clin. Cancer Res. 9, 2335–2341.

    PubMed  CAS  Google Scholar 

  22. Kunstfeld, R., Wickenhauser, G., Michaelis, U., et al. (2003) Paclitaxel encapsulated in cationic liposomes diminishes tumor angiogenesis and melanoma growth in a “humanized” SCID mouse model. J. Invest. Dermatol. 120, 476–482.

    Article  PubMed  CAS  Google Scholar 

  23. Dvorak, H. F., Nagy, J. A., and Dvorak, A. M. (1991) Structure of solid tumors and their vasculature: implications for therapy with monoclonal antibodies. Cancer Cells 3, 77–85.

    PubMed  CAS  Google Scholar 

  24. Shockley, T. R., Lin, K., Nagy, J. A., Tompkins, R. G., Dvorak, H. F., and Yarmush, M. L. (1991) Penetration of tumor tissue by antibodies and other immunoproteins. Ann. NY Acad. Sci. 618, 367–382.

    Article  PubMed  CAS  Google Scholar 

  25. Jain, R. K. (1997) Delivery of molecular and cellular medicine to solid tumors. Microcirculation 4, 1–23.

    Article  PubMed  CAS  Google Scholar 

  26. Kisak, E. T., Coldren, B., Evans, C. A., Boyer, C., and Zasadsinski, J. A. (2003) The vesosome—a multicompartment drug delivery vehicle. Current Med. Chem. 11, 1241–1253.

    Google Scholar 

  27. Meers, P. (2001) Enzyme-activated targeting of liposomes. Adv. Drug Deliv. Rev. 53, 265–272.

    Article  PubMed  CAS  Google Scholar 

  28. Hu, L., Ho, R. J. Y., and Huang, L. (1986) Trypsin induced destabilization of liposomes composed of dioleoylphosphatidylethanolamine and glycorphorin. Biochem. Biophys. Res. Commun. 141, 973–978.

    Article  PubMed  CAS  Google Scholar 

  29. Sarkar, N. R., Rosendahl, T., Krueger, A. B., et al. (2005) “Uncorking” of liposomes by matrix metalloproteinase-9. Chem. Commun., 999–1001.

    Google Scholar 

  30. Lutolf, M. P., Lauer-Fields, J. L., Schmoekel, H. G., et al. (2003) Synthetic matrix metalloproteinase-sensitive hydrogels for the conduction of tissue regeneration: engineering cell-invasion characteristics. Proc. Natl. Acad. Sci. USA 100, 5413–5418.

    Article  PubMed  CAS  Google Scholar 

  31. Chau, Y., Tan, F. E., and Langer, R. (2004) Synthesis and characterization of dextran-peptide-methotrexate conjugates for tumor targeting via mediation by matrix metalloproteinase II and matrix metalloproteinase IX. Bioconjugate Chem. 15, 931–941.

    Article  CAS  Google Scholar 

  32. Pierschbacher, M. D. and Ruoslahti, E. (1987) Influence of stereochemistry of the sequence Arg-Gly-Asp-Xaa on binding specificity in cell adhesion. J. Biol. Chem. 262, 17,297–17,298.

    Google Scholar 

  33. Pakalns, T., Haverstick, K. L., Fields, G. B., McCarthy, J. B., Mooradian, D. L., and Tirrell, M. (1999) Cellular recognition of synthetic peptide amphiphiles in self-assembled monolayer films. Biomaterials 20, 2265–2279.

    Article  PubMed  CAS  Google Scholar 

  34. Lauer, J. L., Gendron, C. M., and Fields, G. B. (1998) Effect of ligand conformation on melanoma cell α3ß1 integrin-mediated signal transduction events: implications for a collagen structural modulation mechanism of tumor cell invasion. Biochemistry 37, 5279–5287.

    Article  PubMed  CAS  Google Scholar 

  35. Fields, G. B., Lauer, J. L., Dori, Y., Forns, P., Yu, Y.-C., and Tirrell, M. (1998) Proteinlike molecular architecture: biomaterial applications for inducing cellular receptor binding and signal transduction. Biopolymers 47, 143–151.

    Article  PubMed  CAS  Google Scholar 

  36. Malkar, N. B., Lauer-Fields, J. L., Borgia, J. A., and Fields, G. B. (2002) Modulation of triple-helical stability and subsequent melanoma cellular responses by single-site substitution of fluoroproline derivatives. Biochemistry 41, 6054–6064.

    Article  PubMed  CAS  Google Scholar 

  37. Li, C., McCarthy, J. B., Furcht, L. T., and Fields, G. B. (1997) An all-D amino acid peptide model of α1(IV)531-543 from type IV collagen binds the α3ß1 integrin and mediates tumor cell adhesion, spreading, and motility. Biochemistry 36, 15,404–15,410.

    CAS  Google Scholar 

  38. Yu, Y.-C., Berndt, P., Tirrell, M., and Fields, G. B. (1996) Self-assembling amphiphiles for construction of protein molecular architecture. J. Am. Chem. Soc. 118, 12,515–12,520.

    CAS  Google Scholar 

  39. Yu, Y.-C., Tirrell, M., and Fields, G. B. (1998) Minimal lipidation stabilizes protein-like molecular architecture. J. Am. Chem. Soc. 120, 9979–9987.

    Article  CAS  Google Scholar 

  40. Forns, P., Lauer-Fields, J. L., Gao, S., and Fields, G. B. (2000) Induction of protein-like molecular architecture by monoalkyl hydrocarbon chains. Biopolymers 54, 531–546.

    Article  PubMed  CAS  Google Scholar 

  41. Borgia, J. A. and Fields, G. B. (2000) Chemical synthesis of proteins. Trends Biotech. 18, 243–251.

    Article  CAS  Google Scholar 

  42. Mammen, M., Choi, S.-K., and Whitesides, G. M. (1998) Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors. Angew. Chem. Int. Ed. 37, 2754–2794.

    Article  Google Scholar 

  43. García, M., Alsina, M. A., Reig, F., and Haro, I. (2000) Liposomes as vehicles for the presentation of a synthetic peptide containing an epitope of hepatitis A virus. Vaccine 18, 276–283.

    Article  Google Scholar 

  44. Dillow, A. K., Ochsenhirt, S. E., McCarthy, J. B., Fields, G. B., and Tirrell, M. (2001) Adhesion of α5ß1 receptors to biomimetic substrates constructed from peptide amphiphiles. Biomaterials 22, 1493–1505.

    Article  CAS  Google Scholar 

  45. Malkar, N. B., Lauer-Fields, J. L., Juska, D., and Fields, G. B. (2003) Characterization of peptide-amphiphiles possessing cellular activation sequences. Biomacromolecules 4, 518–528.

    Article  PubMed  CAS  Google Scholar 

  46. Baronas-Lowell, D., Lauer-Fields, J. L., and Fields, G. B. (2004) Induction of endothelial cell activation by a triple-helical α2ß1 integrin ligand derived from type I collagen α1(I)496-507. J. Biol. Chem. 279, 952–962.

    Article  PubMed  CAS  Google Scholar 

  47. Kokkoli, E., Ochsenhirt, S. E., and Tirrell, M. (2004) Collective and single-molecule interactions of α5ß1 integrins. Langmuir 20, 2397–2404.

    Article  PubMed  CAS  Google Scholar 

  48. Huo, Q., Sui, G., Kele, P., and Leblanc, R. M. (2000) Combinatorial surface chemistry—is it possible? Angew. Chem. Int. Ed. 39, 1854–1857.

    Article  CAS  Google Scholar 

  49. Hartgerink, J. D., Beniash, E., and Stupp, S. I. (2002) Peptide-amphiphile nanofibers: a versatile scaffold for the preparation of self-assembling materials. Proc. Natl. Acad. Sci. USA 99, 5133–5138.

    Article  PubMed  CAS  Google Scholar 

  50. Gore, T., Dori, Y., Talmon, Y., Tirrell, M., and Bianco-Peled, H. (2001) Self-assembly of model collagen peptide amphiphiles. Langmuir 17, 5352–5360.

    Article  CAS  Google Scholar 

  51. Lauer-Fields, J. L., Tuzinski, K. A., Shimokawa, K., Nagase, H., and Fields, G. B. (2000) Hydrolysis of triple-helical collagen peptide models by matrix metalloproteinases. J. Biol. Chem. 275, 13,282–13,290.

    Article  CAS  Google Scholar 

  52. Lauer-Fields, J. L., Nagase, H., and Fields, G. B. (2000) Use of Edman degradation sequence analysis and matrix-assisted laser desorption/ionization mass spectrometry in designing substrates for matrix metalloproteinases. J. Chromatogr. A. 890, 117–125.

    Article  PubMed  CAS  Google Scholar 

  53. Lauer-Fields, J. L., Broder, T., Sritharan, T., Nagase, H., and Fields, G. B. (2001) Kinetic analysis of matrix metalloproteinase triple-helicase activity using fluorogenic substrates. Biochemistry 40, 5795–5803.

    Article  PubMed  CAS  Google Scholar 

  54. Woessner, J. F. and Nagase, H. (2000) Matrix Metalloproteinases and TIMPs. Oxford University Press, Oxford.

    Google Scholar 

  55. Kühn, K. and Eble, J. (1994) The structural bases of integrin-ligand interactions. Trends Cell Biol. 4, 256–261.

    Article  PubMed  Google Scholar 

  56. van der Flier, A. and Sonnenberg, A. (2001) Function and interactions of integrins. Cell Tissue Res. 305, 285–298.

    Article  PubMed  Google Scholar 

  57. Kramer, R. H. and Marks, N. (1989) Identification of intracellular collagen receptor on human melanoma cells. J. Biol. Chem. 264, 4684–4688.

    PubMed  CAS  Google Scholar 

  58. Miles, A. J., Knutson, J. R., Skubitz, A. P. N., Furcht, L. T., McCarthy, J. B., and Fields, G. B. (1995) A peptide model of basement membrane collagen α 1(IV)531-543 binds the α3ß1 integrin. J. Biol. Chem. 270, 29,047–29,050.

    CAS  Google Scholar 

  59. Klein, C. E., Dressel, D., Steinmayer, T., et al. (1991) Integrin α2ß1 is upregulated in fibroblasts and highly aggressive melanoma cell in three-dimensional collagen lattices and mediates the reorganization of type I collagen fibrils. J. Cell Biol. 115, 1427–1436.

    Article  PubMed  CAS  Google Scholar 

  60. Yoshinaga, I. G., Vink, J., Dekker, S. K., Mihm, M.C., Jr., and Byers, H. R. (1993) Role of α3ß1 and α2ß1 integrins in melanoma cell migration, Melanoma Res. 3, 435–441.

    Article  PubMed  CAS  Google Scholar 

  61. Heino, J. (1996) Biology of tumor cell invasion: interplay of cell adhesion and matrix degradation. Int. J. Cancer 65, 717–722.

    Article  PubMed  CAS  Google Scholar 

  62. Mizejewski, G. J. (1999) Role of integrins in cancer: survey of expression patterns. Proc. Soc. Exp. Biol. Med. 222, 124–138.

    Article  PubMed  CAS  Google Scholar 

  63. Golbik, R., Eble, J. A., Ries, A., and Kühn, K. (2000) The spatial orientation of the essential amino acid residues arginine and aspartate within the α1ß1 integrin recognition site of collagen IV has been resolved using fluorescence resonance energy transfer. J. Mol. Biol. 297, 501–509.

    Article  PubMed  CAS  Google Scholar 

  64. Saccá, B., Sinner, E.-K., Kaiser, J., Lübken, C., Eble, J. A., and Moroder, L. (2002) Binding and docking of synthetic heterotrimeric collagen type IV peptides with α1ß1 integrin. ChemBioChem 9, 904–907.

    Article  Google Scholar 

  65. Knight, C. G., Morton, L. F., Onley, D. J., et al. (1998) Identification in collagen type I of an integrin α2ß1-binding site containing an essential GER sequence. J. Biol. Chem. 273, 33,287–33,294.

    CAS  Google Scholar 

  66. Knight, C. G., Morton, L. F., Peachey, A. R., Tuckwell, D. S., Farndale, R. W., and Barnes, M. J. (2000) The collagen-binding A-domains of integrin α1ß1 and α2ß1 recognize the same specific amino acid sequence, GFOGER, in native (triple-helical) collagens. J. Biol. Chem. 275, 35–40.

    Article  PubMed  CAS  Google Scholar 

  67. Emsley, J., Knight, C. G., Farndale, R. W., Barnes, M. J., and Liddington, R. C. (2000) Structural basis of collagen recognition by integrin α2ß1. Cell 101, 47–56.

    Article  PubMed  CAS  Google Scholar 

  68. Lauer-Fields, J. L., Sritharan, T., Stack, M. S., Nagase, H., and Fields, G. B. (2003) Selective hydrolysis of triple-helical substrates by matrix metalloproteinase-2 and -9. J. Biol. Chem. 278, 18,140–18,145.

    CAS  Google Scholar 

  69. Baronas-Lowell, D., Lauer-Fields, J. L., Borgia, J. A., Sferrazza, G. F., Al-Ghoul, M., Minond, D., and Fields, G. B. (2004) Differential modulation of human melanoma cell metalloproteinase expression by α2ß1 integrin and CD44 triple-helical ligands derived from type IV collagen. J. Biol. Chem. 279, 43,503–43,513.

    Article  CAS  Google Scholar 

  70. Miles, A. J., Skubitz, A. P. N., Furcht, L. T., and Fields, G. B. (1994) Promotion of cell adhesion by single-stranded and triple-helical peptide models of basement membrane collagen α1(IV)531-543: evidence for conformationally dependent and conformationally independent type IV collagen cell adhesion sites. J. Biol. Chem. 269, 30,939–30,945.

    CAS  Google Scholar 

  71. Faassen, A. E., Drake, S. L., Iida, J., Knutson, J. R., and McCarthy, J. B. (1992) Mechanisms of normal cell adhesion to the extracellular matrix and alterations associated with tumor invasion and metastasis. Adv. Pathol. Lab. Med 5, 229–259.

    Google Scholar 

  72. Iida, J., Meijne, A. M. L., Knutson, J. R., Furcht, L. T., and McCarthy, J. B. (1996) Cell surface chondroitin sulfate proteoglycans in tumor cell adhesion, motility and invasion. Seminars Cancer Biol. 7, 155–162.

    Article  CAS  Google Scholar 

  73. Herbold, K. W., Zhou, J., Haggerty, J. G., and Milstone, L. M. (1996) CD44 expression on epidermal melanocytes. J. Invest. Dermatol. 106, 1230–1235.

    Article  PubMed  CAS  Google Scholar 

  74. Screaton, G. R., Bell, M. V., Jackson, D. G., Cornelis, F. B., Gerth, U., and Bell, J. I. (1992) Genomic structure of DNA encoding the lymphocyte homing receptor CD44 reveals at least 12 alternatively spliced exons. Proc. Natl. Acad. Sci. USA 89, 12,160–12,164.

    Article  CAS  Google Scholar 

  75. Naor, D., Slonov, R. V., and Ish-Shalom, D. (1997) CD44: structure, function, and association with the malignant process, in Advances in Cancer Research (Vande Woude, G. F. and Klein, G., eds.). Academic, Orlando, FL: pp. 241–319.

    Google Scholar 

  76. Lesley, J. and Hyman, R. (1998) CD44 structure and function. Frontiers Biosci. 3, 616–630.

    Google Scholar 

  77. Lauer-Fields, J. L., Malkar, N. B., Richet, G., Drauz, K., and Fields, G. B. (2003) Melanoma cell CD44 interaction with the α1(IV)1263-1277 region from basement membrane collagen is modulated by ligand glycoslyation. J. Biol. Chem. 278, 14,321–14,330.

    CAS  Google Scholar 

  78. Fields, C. G., Mickelson, D. J., Drake, S. L., McCarthy, J. B., and Fields, G. B. (1993) Melanoma cell adhesion and spreading activities of a synthetic 124-residue triple-helical “mini-collagen”. J. Biol. Chem. 268, 14,153–14,160.

    CAS  Google Scholar 

  79. Sweeney, S. M., DiLullo, G., Slater, S. J., et al. (2003) Angiogenesis in collagen I requires α2ß1 ligation of a GFP*GER sequence, and possibly p38 MAPK and focal adhesion disassembly. J. Biol. Chem. 278, 30,516–30,524.

    Article  CAS  Google Scholar 

  80. Xu, Y., Gurusiddappa, S., Rich, R. L., et al. (2000) Multiple binding sites in collagen type I for the integrins α1ß1 and α2ß1., J. Biol. Chem. 275, 38,981–38,989.

    CAS  Google Scholar 

  81. Tu, R., Mohanty, K., and Tirrell, M. (2004) Liposomal targeting through peptide-amphiphile functionalization. Am. Pharm. Rev. 7(2), 36–41.

    CAS  Google Scholar 

  82. Dori, Y., Bianco-Peled, H., Satija, S. K., Fields, G. B., McCarthy, J. B., and Tirrell, M. (2000) Ligand accessibility as a means to control cell response to bioactive bilayer membranes. J. Biomed. Mater. Res. 50, 75–81.

    Article  PubMed  CAS  Google Scholar 

  83. Torchilin, V. P., Rammohan, R., Weissig, V., and Levchenko, T. S. (2001) TAT peptide on the surface of liposomes affords their efficient intracellular delivery even at low temperature and in the presence of metabolic inhibitors. Proc. Natl. Acad. Sci. USA 98, 8786–8791.

    Article  PubMed  CAS  Google Scholar 

  84. Berndt, P., Fields, G. B., and Tirrell, M. (1995) Synthetic lipidation of peptides and amino acids: monolayer structure and properties. J. Am. Chem. Soc. 117, 9515–9522.

    Article  CAS  Google Scholar 

  85. King, D. S., Fields, C. G., and Fields, G. B. (1990) A cleavage method which minimizes side reactions following Fmoc solid phase peptide synthesis. Int. J. Peptide Protein Res. 36, 255–266.

    Article  CAS  Google Scholar 

  86. Fields, C. G. and Fields, G. B. (1993) Minimization of tryptophan alkylation following 9-fluorenylmethoxycarbonyl solid-phase peptide synthesis. Tetrahedron Lett. 34, 6661–6664.

    Article  CAS  Google Scholar 

  87. Fields, C. G., Lovdahl, C. M., Miles, A. J., Matthias-Hagen, V. L., and Fields, G. B. (1993) Solid-phase synthesis and stability of triple-helical peptides incorporating native collagen sequences. Biopolymers 33, 1695–1707.

    Article  PubMed  CAS  Google Scholar 

  88. Grab, B., Miles, A. J., Furcht, L. T., and Fields, G. B. (1996) Promotion of fibroblast adhesion by triple-helical peptide models of type I collagen-derived sequences. J. Biol. Chem. 271, 12,234–12,240.

    CAS  Google Scholar 

  89. Yu, Y.-C., Roontga, V., Daragan, V. A., Mayo, K. H., Tirrell, M., and Fields, G. B. (1999) Structure and dynamics of peptide-amphiphiles incorporating triple-helical proteinlike molecular architecture. Biochemistry 38, 1659–1668.

    Article  PubMed  CAS  Google Scholar 

  90. Chapter 1 (2002), in Liposome Methods and Protocols, Methods in Molecular Biology Vol. 199 (Basu, S. B. and Basu, M., eds.). Humana, NJ.

    Google Scholar 

  91. Hope, M. J., Bally, M. B., Webb, G., and Cullis, P. R. (1985) Production of large unilamellar vesicles by a rapid extrusion procedure: characterization of size distribution, trapped volume and ability to maintain a membrane potential. Biochim. Biophys. Acta 812, 55–65.

    Article  CAS  Google Scholar 

  92. Drummond, D. C., Meyer, O., Hong, K., Kirpotin, D. B., and Papahadjopoulos, D. (1999) Optimizing liposomes for delivery of chemotherapeutic agents to solid tumors. Pharmacol. Rev. 51, 691–744.

    PubMed  CAS  Google Scholar 

  93. Nagayasu, A., Uchiyama, K., and Kiwada, H. (1999) The size of liposomes: a factor which affects their targeting efficiency to tumors and therapeutic activity of liposomal antitumor drugs. Adv. Drug Deliv. Rev. 40, 75–87.

    Article  PubMed  CAS  Google Scholar 

  94. Charrois, G. J. R. and Allen, T. M. (2003) Rate of biodistribution of STEALTH liposomes to tumor and skin: influence of liposome diameter and implications for toxicity and therapeutic activity. Biochim. Biophys. Acta 1609, 102–108.

    Article  PubMed  CAS  Google Scholar 

  95. Balsara, N. P., Stepanek, P., Lodge, T. P., and Tirrell, M. (1991) Dynamic light scattering from microstructured block copolymer solutions. Macromolecules 24, 6227–6230.

    Article  CAS  Google Scholar 

  96. Dan, N., and Tirrell, M. (1993) Self-assembly of block copolymers with a strongly charged and a hydrophobic block in a selective, polar solvent: micelles and adsorbed layers. Macromolecules 26, 4310–4315.

    Article  CAS  Google Scholar 

  97. Guenoun, P., Delsanti, M., Gazeau, D., et al. (1998) Structural properties of charged diblock copolymer solutions. Eur. Phys. J. B 1, 77–86.

    Article  CAS  Google Scholar 

  98. Guenoun, P., Davis, H. T., Doumaux, H. A., et al. (2000) Polyelectrolyte micelles: self-diffusion and electron microscopy studies, Langmuir 16, 4436–4440.

    Article  CAS  Google Scholar 

  99. Muller, F., Delsanti, M., Auvray, L., et al. (2000) Ordering of urchin-like charged copolymer micelles: electrostatic, packing and polyelectrolyte correlations. Eur. Phys. J. E 3, 45–53.

    Article  CAS  Google Scholar 

  100. Zuidam, N. J., de Vrueh, R., and Crommelin, D. J. A. (2003) Characterization of liposomes, in Liposomes: A Practical Approach, Second Edition (Torchilin, V. P. and Weissig, V., eds.). Oxford University Press, Oxford, UK: pp. 31–78.

    Google Scholar 

  101. Backer, M. V., Gaynutdinov, T. I., Patel, V., Jehning, B. T., Myshkin, E., and Backer, J. M. (2004) Adapter protein for site-specific conjugation of payloads for targeted drug delivery. Bioconjugate Chem. 15, 1021–1029.

    Article  CAS  Google Scholar 

  102. Fields, G. B., Lauer-Fields, J. L., Liu, R.-Q., and Barany, G. (2001) Principles and practice of solid-phase peptide synthesis, in Synthetic Peptides: A User’s Guide, 2nd Edition (Grant, G. A., ed.). W.H. Freeman & Co., New York: pp. 93–219.

    Google Scholar 

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Acknowledgments

We gratefully acknowledge support of this work by the National Institutes of Health (CA 77402 and CA 98799 to GBF, EB 000289 to GBF/MT). In addition, this work was supported at UC Santa Barbara in part by the National Science Foundation under NSF awards NSF/MRSEC DMR-0080034, NSF/NIRT CTS-0103516, and the Army Research Office through the Institute for Collaborative Biotechnologies, and at Florida Atlantic University by the Center of Excellence in Biomedical and #P200507).

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Authors and Affiliations

  1. Department of Chemistry & Biochemistry, Florida Atlantic University, Boca Raton, FL

    Evonne M. Rezler & David R. Khan

  2. College of Engineering, University of California, Santa Barbara, CA

    Raymond Tu & Matthew Tirrell

  3. Department of Chemistry & Biochemistry and Center for Molecular Biology & Biotechnology, Florida Atlantic University, Boca Raton, FL

    Gregg B. Fields

Authors
  1. Evonne M. Rezler
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  2. David R. Khan
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  3. Raymond Tu
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  4. Matthew Tirrell
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  5. Gregg B. Fields
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Editors and Affiliations

  1. Department of Chemistry and Biochemistry, Florida Atlantic University, Boca Raton, FL

    Gregg B. Fields

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© 2007 Humana Press Inc.

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Rezler, E.M., Khan, D.R., Tu, R., Tirrell, M., Fields, G.B. (2007). Peptide-Mediated Targeting of Liposomes to Tumor Cells. In: Fields, G.B. (eds) Peptide Characterization and Application Protocols. Methods in Molecular Biology™, vol 386. Humana Press. https://doi.org/10.1007/978-1-59745-430-8_10

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  • DOI: https://doi.org/10.1007/978-1-59745-430-8_10

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-550-7

  • Online ISBN: 978-1-59745-430-8

  • eBook Packages: Springer Protocols

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