Binding of novel peptide inhibitors of type IV collagenases to phospholipid membranes and use in liposome targeting to tumor cells in vitro.

摘要: We have recently described a novel cyclic peptide inhibitor CTTHWGFTLC (CTT) for matrix metalloproteinases (MMP)-2 and MMP-9, also called type IV collagenases or gelatinases (E. Koivunen et al., NAT: BIOTECHNOL:, 17: 768-774, 1999). As indicated by its amino acid composition, CTT is hydrophobic, partitioning into phospholipid films could be verified the monolayer technique. Augmented fluorescence emission anisotropy (from 0.064 to 0.349) reduced collisional quenching I(-) of Trp residue in was evident presence unilamellar phosphatidylcholine/phosphatidylethanolamine liposomes, revealing association with lipid bilayers. Gelatinases are potential targets therapeutic intervention cancer, inhibitors these enzymes can prevent tumor progression animal models. enhanced 3- 4-fold cellular uptake liposome-encapsulated water-soluble fluorescent marker, rhodamine B gelatinase-expressing cells. Gelatinase targeting seems essential, as modified peptides that were less potent gelatinase efficient promoting liposomes. killing ( approximately 4-fold) U937 leukemia HT1080 sarcoma cells obtained CTT-enhanced delivery Adriamycin-containing compared control liposomes administered without peptide. These results suggest utility small targeted cancer therapy.