Each normal organ and pathological condition contains organ- or disease-specific molecular tags on its vasculature that constitute a vascular ‘zip code’ system. Tissue-selective tumour metastasis may also depend on vascular addresses. We have used phage display peptide libraries to map disease-specific differences in the vasculature. By using this technology, we have isolated several peptides which are targeted specifically to tumour blood vessels, lymphatic vessels and/or tumour cells. Some of the tumour-homing peptides recognize common angiogenesis markers and are capable of binding to several types of tumour, whereas other peptides recognize tumour-type-specific differences. We have also shown that the vasculature of a pre-malignant lesion differs from that of a full-blown tumour and also from the vasculature of the corresponding normal organ. Our peptides have revealed molecules that act as novel biomarkers of this vascular heterogeneity. Interestingly, some of our homing peptides are able to penetrate the target cells. This internalization differs from that of the Tat, penetratins and other related peptides in that our peptides enter the cell in a cell-type-specific manner. These peptides appear to be able to concentrate in the target tissue, making them particularly efficient delivery vectors for the targeting of drugs, other therapeutic moieties and imaging agents.

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