Vascular targeting with phage peptide libraries.
We have developed an in vivo selection system in which phage capable of selective homing to different tissues are recovered from a phage display peptide library following intravenous administration. Using this strategy, we have isolated several organ and tumor-homing peptides. We have shown that each of those peptides binds to different receptors that are selectively expressed on the vasculature of the target tissue. The tumor-homing peptides bind to receptors that are upregulated in tumor angiogenic vasculature. Targeted delivery of doxorubicin to angiogenic vasculature using these peptides in animal models decreased toxicity and increased the therapeutic efficacy of the drug. Vascular targeting may facilitate the development of other treatment strategies that rely on inhibition of angiogenesis and lead to advances in cancer treatment. Our technology is also likely to extend the potential for targeting of drugs, genes, and radionuclides in the context of many diseases.
Pasqualini
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La Jolla Cancer Research Center, Burnham Institute, CA 92037, USA.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage; D001435:Bacteriophages; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology*; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000378:metabolism; D019151:Peptide Library; D011485:Protein Binding; D011991:Receptors, Virus / Q000378:metabolism; D015854:Up-Regulation; D014764:Viral Proteins
D000903:Antibiotics, Antineoplastic; D019151:Peptide Library; D011991:Receptors, Virus; D014764:Viral Proteins; D004317:Doxorubicin