Liposomes modified with a synthetic Arg-Gly-Asp mimetic inhibit lung metastasis of B16BL6 melanoma cells

Administration of large amounts of synthetic peptides based on the Arg-Gly-Asp (RGD) sequence has been shown to suppress tumor metastasis. To overcome the rapid degradation of peptides in the circulation, an RGD mimetic, L-arginyl-6-aminohexanoic acid (NOK), was synthesized and conjugated with phosp...

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Bibliographic Details
Published in:Life sciences (1973) 2000-12, Vol.68 (3), p.273-281
Main Authors: Kurohane, Kohta, Namba, Yukihiro, Oku, Naoto
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - administration & dosage
Antineoplastic Agents - chemical synthesis
Arg-Gly-Asp
B16BL6 melanoma
Cell Adhesion - drug effects
Drug Carriers
Fibronectins - metabolism
Liposome
Liposomes
Lung Neoplasms - prevention & control
Lung Neoplasms - secondary
Male
Melanoma, Experimental - pathology
Melanoma, Experimental - prevention & control
Metastasis
Mice
Mice, Inbred C57BL
Neoplasm Metastasis - prevention & control
Oligopeptides - administration & dosage
Oligopeptides - chemical synthesis
Phosphatidylethanolamines
Tumor Cells, Cultured
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Summary:Administration of large amounts of synthetic peptides based on the Arg-Gly-Asp (RGD) sequence has been shown to suppress tumor metastasis. To overcome the rapid degradation of peptides in the circulation, an RGD mimetic, L-arginyl-6-aminohexanoic acid (NOK), was synthesized and conjugated with phosphatidylethanolamine (PE) (NOK-PE) for liposomalization. Cell adhesion assays revealed that B16BL6 murine melanoma cells adhered to immobilized NOK-PE. This adhesion was inhibited by addition of either soluble RGDS or NOK at similar concentration in a dose-dependent manner. Administration of NOK-PE liposomes (equivalent to ca. 500μg RGD peptides) via the tail vein completely inhibited lung colonization of B16BL6 cells. The same dose of soluble NOK was not effective in inhibition of the tumor metastasis. In addition, injection of NOK-PE liposomes via the tail vein inhibited spontaneous lung metastasis of B16BL6 cells from the primary tumor site in the hind footpad. These results suggest that NOK, a structural mimetic of RGD, is capable of suppressing metastasis by blockade of the binding of the integrins present on tumor cells to the RGD-containing extracellular matrix.
ISSN:0024-3205
1879-0631
DOI:10.1016/S0024-3205(00)00938-3