Molecularly targeted nanocarriers deliver the cytolytic peptide melittin specifically to tumor cells in mice, reducing tumor growth

Journal of Clinical Investigation

Volumn 119, Issue 9, 2009, Pages 2830-2842

  Soman, Neelesh R ^a   Baldwin, Steven L ^a   Hu, Grace ^a   Marsh, Jon N ^a   Lanza, Gregory M ^a   Heuser, John E ^a   Arbeit, Jeffrey M ^a   Wickline, Samuel A ^a   Schlesinger, Paul H ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DOXORUBICIN; FLUOROCARBON; MELITTIN; NANOCARRIER; NANOPARTICLE; PACLITAXEL;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; CANCER GROWTH; CELL SPECIFICITY; CONTROLLED STUDY; CYTOLYSIS; CYTOTOXICITY; DYSPLASIA; ENDOTHELIUM CELL; HUMAN; HUMAN CELL; IN VIVO STUDY; LIPID MONOLAYER; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; ANTINEOPLASTIC AGENTS; BREAST NEOPLASMS; CELL LINE, TUMOR; DRUG CARRIERS; FEMALE; HUMANS; LIPOSOMES; MELANOMA, EXPERIMENTAL; MELITTEN; MICE; MICE, INBRED C57BL; MICE, NUDE; MICROSCOPY, ELECTRON, TRANSMISSION; NANOPARTICLES; TISSUE DISTRIBUTION;

EID: 70349220917     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI38842     Document Type: Article

References (74)

1. Giuliani, A., Pirri, G., and Nicoletto, S. 2007. Antimicrobial peptides: an overview of a promising class of therapeutics. Central European J. Biol. 2:1-33. (Pubitemid 46450753)
2. Papo, N., and Shai, Y. 2005. Host defense peptides as new weapons in cancer treatment. Cell. Mol. Life Sci. 62:784-790. (Pubitemid 40655628)
3. Hancock, R.E., and Sahl, H.G. 2006. Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 24:1551-1557.
4. Hoskin, D.W., and Ramamoorthy, A. 2008. Studies on anticancer activities of antimicrobial peptides. Biochim. Biophys. Acta. 1778:357-375.
5. Zhang, L., and Falla, T.J. 2006. Antimicrobial peptides: Therapeutic potential. Expert Opin. Pharmacother. 7:653-663.
6. Leuschner, C., and Hansel, W. 2004. Membrane disrupting lytic peptides for cancer treatments. Curr. Pharm. Des. 10:2299-2310. (Pubitemid 38855038)
7. Hansel, W., Enright, F., and Leuschner, C. 2007. Destruction of breast cancers and their metastases by lytic peptide conjugates in vitro and in vivo. Mol. Cell. Endocrinol. 260-262:183-189. (Pubitemid 44792362)
8. Hansel, W., Leuschner, C., and Enright, F. 2007. Conjugates of lytic peptides and lhrh or betacg target and cause necrosis of prostate cancers and metastases. Mol. Cell. Endocrinol. 269:26-33. (Pubitemid 46483829)
9. Kumar, C.S., et al. 2004. Efficacy of lytic peptide-bound magnetite nanoparticles in destroying breast cancer cells. J. Nanosci. Nanotechnol. 4:245-249.
10. Hui, L., Leung, K., and Chen, H.M. 2002. The combined effects of antibacterial peptide cecropin a and anti-cancer agents on leukemia cells. Anticancer Res. 22:2811-2816. (Pubitemid 36069317)
11. Lincke, C.R., et al. 1990. Multidrug resistance phenotype of human BRO melanoma cells transfected with a wild-type human mdr1 complementary DNA. Cancer Res. 50:1779-1785.
12. Ohsaki, Y., Gazdar, A.F., Chen, H.C., and Johnson, B.E. 1992. Antitumor activity of magainin analogues against human lung cancer cell lines. Cancer Res. 52:3534-3538.
13. Bechinger, B. 1997. Structure and functions of channel-forming peptides: Magainins, cecropins, melittin and alamethicin. J. Membr. Biol. 156:197-211. (Pubitemid 27208423)
14. Tosteson, M.T., and Tosteson, D.C. 1981. The sting: Melittin forms channels in lipid bilayers. Biophys. J. 36:109-116.
15. DeGrado, W.F., Musso, G.F., Lieber, M., Kaiser, E.T., and Kezdy, F.J. 1982. Kinetics and mechanism of hemolysis induced by melittin and by a synthetic melittin analogue. Biophys. J. 37:329-338.
16. Lee, M.-T., Chen, F.-Y., and Huang, H.W. 2004. Energetics of pore formation induced by membrane active peptides. Biochemistry. 43:3590-3599.
17. Yang, L., Harroun, T.A., Weiss, T.M., Ding, L., and Huang, H.W. 2001. Barrel-stave model or toroidal model? A case study on melittin pores. Biophys. J. 81:1475-1485. (Pubitemid 32783588)
18. Lee, M.-T., Hung, W.-C., Chen, F.-Y., and Huang, H.W. 2008. Mechanism and kinetics of pore formation in membranes by water-soluble amphipathic peptides. Proc. Natl. Acad. Sci. U. S. A. 105:5087-5092.
19. Soman, N.R., et al. 2008. Synthesis and characterization of stable fluorocarbon nanostructures as drug delivery vehicles for cytolytic peptides. Nano Lett. 8:1131-1136.
20. Hu, G., et al. 2007. Imaging of Vx-2 rabbit tumors with ανβ3-integrin-targeted In nanoparticles. Int. J. Cancer. 120:1951-1957.
21. Lanza, G.M., et al. 2002. Molecular imaging and targeted drug delivery with a novel, ligand-directed paramagnetic nanoparticle technology. Acad. Radiol. 9(Suppl. 2):S330-S331.
22. Partlow, K.C., Lanza, G.M., and Wickline, S.A. 2008. Exploiting lipid raft transport with membrane targeted nanoparticles: a strategy for cytosolic drug delivery. Biomaterials. 29:3367-3375.
23. Schmieder, A.H., et al. 2008. Three-dimensional MR mapping of angiogenesis with α5β1(ανβ3)-targeted theranostic nanoparticles in the MDA-MB-435 xenograft mouse model. FASEB J. 22:4179-4189.
24. Winter, P.M., et al. 2003. Molecular imaging of angiogenesis in nascent Vx-2 rabbit tumors using a novel ανβ3-targeted nanoparticle and 1.5 tesla magnetic resonance imaging. Cancer Res. 63:5838-5843.
25. Blondelle, S.E., and Houghten, R.A. 1991. Probing the relationships between the structure and haemolytic activity of melittin with a complete set of leucine substitution analogs. Pept. Res. 4:12-18.
26. Habermann, E., and Zeuner, G. 1971. Comparative studies of native and synthetic melittins. Naunyn Schmiedebergs Arch. Pharmakol. 270:1-9.
27. Schnell, M., Hardy, C., Hawley, M., Propert, K., and Wilson, J. 2002. Effect of blood collection technique in mice on clinical pathology parameters. Hum. Gene. Ther. 13:155-161. (Pubitemid 34075179)
28. Desai, N., et al. 2006. Increased antitumor activity, intratumor paclitaxel concentrations, and endothelial cell transport of cremophor-free, albumin-bound paclitaxel, ABI-007, compared with cremophor-based paclitaxel. Clin. Cancer Res. 12:1317-1324. (Pubitemid 43342524)
29. Laginha, K., Verwoert, S., Charrois, G., and Allen, T. 2005. Determination of doxorubicin levels in whole tumor and tumor nuclei in murine breast cancer tumors. Clin. Cancer Res. 11:6944-6949. (Pubitemid 41428752)
30. Hamzah, J., et al. 2008. Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature. 453:410-414. (Pubitemid 351693122)
31. Culp, W., et al. 2006. Proteomic analysis of tumor establishment and growth in the B16-F10 mouse melanoma model. J. Proteome Res. 5:1332-1343. (Pubitemid 43865804)
32. Alizadeh, H., et al. 2003. Reduction of liver metastasis of intraocular melanoma by interferon-beta gene transfer. Invest. Ophthalmol. Vis. Sci. 44:3042-3051. (Pubitemid 36759771)
33. Mano, M., Cassidy, J., and Canney, P. 2005. Liver metastases from breast cancer: management of patients with significant liver dysfunction. Cancer Treat. Rev. 31:35-48. (Pubitemid 40246989)
34. Harris, T.D., et al. 2003. Design, synthesis, and evaluation of radiolabeled integrin alpha v beta 3 receptor antagonists for tumor imaging and radiotherapy. Cancer Biother. Radiopharm. 18:627-641.
35. Schmieder, A., et al. 2005. Molecular MR imaging of melanoma angiogenesis with αvβ3-targeted paramagnetic nanoparticles. Magn. Reson. Med. 53:621-627.
36. Winter, P., et al. 2008. Minute dosages of αvβ3-targeted fumagillin nanoparticles impair Vx-2 tumor angiogenesis and development in rabbits. FASEB J. 22:2758-2767.
37. Neubauer, A.M., et al. 2008. Nanoparticle pharmacokinetic profiling in vivo using magnetic resonance imaging. Magn. Reson. Med. 60:1353-1361.
38. Ahrens, E., Flores, R., Xu, H., and Morel, P. 2005. In vivo imaging platform for tracking immunotherapeutic cells. Nat. Biotechnol. 23:983-987. (Pubitemid 41114032)
39. Partlow, K., et al. 2007. F magnetic resonance imaging for stem/progenitor cell tracking with multiple unique perfluorocarbon nanobeacons. FASEB J. 21:1647-1654. (Pubitemid 46855610)
40. Falck, E., Rog, T., Karttunen, M., and Vattulainen, I. 2008. Lateral diffusion in lipid membranes through collective flows. J. Am. Chem. Soc. 130:44-45.
41. Raghuraman, H., and Chattopadhyay, A. 2007. Orientation and dynamics of melittin in membranes of varying composition utilizing NBD fluorescence. Biophys. J. 92:1271-1283. (Pubitemid 46203188)
42. Christenson, E., Merlin, S., Saito, M., and Schlesinger, P. 2008. Cholesterol effects on bax pore activation. J. Mol. Biol. 381:1168-1183.
43. Li, Y.C., Park, M.J., Ye, S.K., Kim, C.W., and Kim, Y.N. 2006. Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents. Am. J. Pathol. 168:1107-1118.
44. Lucken-Ardjomande, S., Montessuit, S., and Martinou, J.-C. 2007. Bax activation and stress-induced apoptosis delayed by the accumulation of cholesterol in mitochondrial membranes. Cell Death Differ. 15:484-493. (Pubitemid 351267299)
45. Arbeit, J., Munger, K., Howley, P., and Hanahan, D. 1994. Progressive squamous epithelial neoplasia in K14-human papillomavirus type 16 transgenic mice. J. Virol. 68:4358-4368. (Pubitemid 24183029)
46. Bechinger, B., and Lohner, K. 2006. Detergent-like actions of linear amphipathic cationic antimicrobial peptides. Biochim. Biophys. Acta. 1758:1529-1539. (Pubitemid 44436087)
47. Vetter, R., Visscher, P., and Camazine, S. 1999. Mass envenomations by honey bees and wasps. West. J. Med. 170:223-227. (Pubitemid 32612758)
48. Vogel, H., and Jahnig, F. 1985. Fast and slow orientational fluctuations in membranes. Proc. Natl. Acad. Sci. U. S. A. 82:2029-2033. (Pubitemid 15060833)
49. Certo, M., et al. 2006. Mitochondria primed by death signals determine cellular addiction to antiapoptotic BCL-2 family members. Cancer Cell. 9:351-365. (Pubitemid 43668734)
50. Deng, J., Carlson, N., Takeyama, K., Cin, P.D., Shipp, M., and Letai, A. 2007. BH3 profiling identifies three distinct classes of apoptotic blocks to predict response to ABT-737 and conventional chemotherapeutic agents. Cancer Cell. 12:171-185. (Pubitemid 47199122)
51. Murphy, E., et al. 2008. Nanoparticle-mediated drug delivery to tumor vasculature suppresses metastasis. Proc. Natl. Acad. Sci. U. S. A. 105:9343-9348.
52. Beekman, K., et al. 2006. Phase II evaluations of cilengitide in asymptomatic patients with androgen-independent prostate cancer: scientific rationale and study design. Clin. Genitourin. Cancer. 4:299-302. (Pubitemid 43779890)
53. Cianfrocca, M.E., et al. 2006. Phase 1 trial of the antiangiogenic peptide ATN-161 (Ac-PHSCN-NH2), a beta integrin antagonist, in patients with solid tumours. Br. J. Cancer. 94:1621-1626.
54. Martin, P.L., et al. 2005. Absence of adverse effects in cynomolgus macaques treated with CNTO 95, a fully human anti-alphav integrin monoclonal antibody, despite widespread tissue binding. Clin. Cancer Res. 11:6959-6965.
55. Mcneel, D.G., et al. 2005. Phase I trial of a monoclonal antibody specific for alphavbeta3 integrin (MEDI-522) in patients with advanced malignancies, including an assessment of effect on tumor perfusion. Clin. Cancer Res. 11:7851-7860.
56. Mullamitha, S.A., et al. 2007. Phase I evaluation of a fully human anti-alphav integrin monoclonal antibody (cnto 95) in patients with advanced solid tumors. Clin. Cancer Res. 13:2128-2135.
57. Nabors, B.L., et al. 2007. Phase I and correlative biology study of cilengitide in patients with recurrent malignant glioma. J. Clin. Oncol. 25:1651-1657.
58. Kemeny, D., Harries, M., Youlten, L., Mackenzie-Mills, M., and Lessof, M. 1983. Antibodies to purified bee venom proteins and peptides. I. development of a highly specific RAST for bee venom antigens and its application to bee sting allergy. J. Allergy Clin. Immunol. 71:505-514.
59. Kemeny, D., MacKenzie-Mills, M., Harries, M., Youlten, L., and Lessof, M. 1983. Antibodies to purified bee venom proteins and peptides. II. a detailed study of changes in IgE and IgG antibodies to individual bee venom antigens. J. Allergy Clin. Immunol. 72:376-385.
60. Nordvall, S., Uhlin, T., Einarsson, R., Johansson, S., and Ohman, S. 1984. Bee keepers IgG and IgE antibody responses to bee venom studied by means of crossed radioimmunoelectrophoresis. Clin. Allergy. 14:341-350. (Pubitemid 14086312)
61. Brooks, P. C., Clark, R. A., and Cheresh, D. A. 1994. Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science. 264:569-571.
62. Stupack, D.G., and Cheresh, D.A. 2002. ECM remodeling regulates angiogenesis: endothelial integrins look for new ligands. Sci. STKE. 2002:PE7.
63. Pasqualini, R., Koivunen, E., and Ruoslahti, E. 1997. Alpha v integrins as receptors for tumor targeting by circulating ligands. Nat. Biotechnol. 15:542-546. (Pubitemid 27251571)
64. Nativo, P., Prior, I.A., and Brust, M. 2008. Uptake and intracellular fate of surface-modified gold nanoparticles. ACS Nano. 2:1639-1644.
65. Gratton, S.E., et al. 2008. The effect of particle design on cellular internalization pathways. Proc. Natl. Acad. Sci. U. S. A. 105:11613-11618.
66. Tu, W.-C., Wu, C.-C., Hsieh, H.-L., Chen, C.-Y., and Hsu, S.-L. 2008. Honeybee venom induces calcium-dependent but caspase-independent apoptotic cell death in human melanoma A2058 cells. Toxicon. 52:318-329.
67. Chu, S., et al. 2007. Phospholipase A2-independent Ca entry and subsequent apoptosis induced by melittin in human MG63 osteosarcoma cells. Life Sci. 80:364-369. (Pubitemid 44958723)
68. Kaufman, R. 1996. Emulsions and emulsion stability. Marcel Dekker. New York, New York, USA. 343-367.
69. Flaim, S.F. 1994. Pharmacokinetics and side effects of perfluorocarbon-based blood substitutes. Artif. Cells Blood Substit. Immobil. Biotechnol. 22:1043-1054. (Pubitemid 24291535)
70. Riess, J. 1984. Reassessment of criteria for the selection of perfluorochemicals for second-generation blood substitutes: analysis of structure/property relationships. Artificial Organs. 8:44-56. (Pubitemid 14126441)
71. Riess, J., and Le Blanc, M. 1978. Perfluoro compounds as blood substitutes. Angewandte Chemie. 17:621-634. (Pubitemid 9390606)
72. Winter, P.M., et al. 2006. Endothelial alpha(v)beta3 integrin-targeted fumagillin nanoparticles inhibit angiogenesis in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 26:2103-2109.
73. Saito, M., Korsmeyer, S.J., and Schlesinger, P.H. 2000. Bax dependent cytochrome-c transport reconstituted in pure liposomes. Nat. Cell Biol. 2:553-555. (Pubitemid 30707175)
74. Heuser, J. 2005. Deep-etch EM reveals that the early poxvirus envelope is a single membrane bilayer stabilized by a geodetic honeycomb surface coat. J. Cell Biol. 169:269-283. (Pubitemid 40656565)