Abstract
A water soluble polymer containing cell adhesive Arg-Gly-Asp- Ser (RGDS) sequence, i.e., poly(carboxyethylmethacrylamide-RGDS) conjugate [poly(CEMA-RGDS)], was synthesized. Poly(CEMA-RGDS) inhibited lung metastasis of B16-BL6 melanoma cells in a dose-dependent manner (20-1000 μg) and liver metastasis of L5178YML25 lymphoma cells. A mixture of poly- (CEMA) and RGDS peptide or poly(CEMA) alone did not show any inhibitory effect on lung metastasis. The Gly-Arg-Gly-Asp-Ser (GRGDS) peptide required high doses (3000 μ g) to obtain a sufficient antimetastatic effect. An in vitro study showed that poly(CEMA-RGDS) as well as RGDS + poly(CEMA) gave similar inhibition of B16-BL6 cell invasion into reconstituted basement mem brane Matrigel. Intermittent i.v. administration of poly(CEMA-RGDS) after in oculation with B16-BL6 cells caused significant inhibition of spontaneous lung metastasis as compared with the multiple administration of RGDS, poly- (CEMA) or untreated control. These results demonstrate that the conjugation
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