A growth factor antagonist as a targeting agent for sterically stabilized liposomes in human small cell lung cancer

The ability of a growth factor antagonist, [D-Arg(6),D-Trp(7.9)-N(me)Phe(8) ]-substance P(6-11), named antagonist G, to selectively target polyethylene glycol-grafted liposomes (known as sterically stabilized liposomes) to a h uman classical small cell lung cancer (SCLC) cell line, H69, was examined. Our results showed that radiolabeled antagonist G-targeted sterically stabi lized liposomes (SLG) bound to H69 cells with higher avidity than free anta gonist G and were internalized (reaching a maximum of 13000 SLG/cell), main ly through a receptor-mediated process, likely involving clathrin-coated pi ts. This interaction was confirmed by confocal microscopy to be peptide- an d cell-specific. Moreover, it was shown that SLG significantly improved the nuclear delivery of encapsulated doxorubicin to the target cells, increasi ng the cytotoxic activity of the drug over non-targeted liposomes. In mice, [I-125]tyraminylinulin-containing SLG were long circulating, with a half-l ife of 13 h. Use of peptides like antagonist G to promote binding and inter nalization of sterically stabilized liposomes, with their accompanying drug loads, i.e., anticancer drugs, genes or antisense oligonucleotides, into t arget cells has the potential to improve therapy of SCLC. (C) 2001 Elsevier Science B.V. All rights reserved.