Cancer treatment by targeted drug delivery to tumor vasculature in a mouse model.
In vivo selection of phage display libraries was used to isolate peptides that home specifically to tumor blood vessels. When coupled to the anticancer drug doxorubicin, two of these peptides-one containing an alphav integrin-binding Arg-Gly-Asp motif and the other an Asn-Gly-Arg motif-enhanced the efficacy of the drug against human breast cancer xenografts in nude mice and also reduced its toxicity. These results indicate that it may be possible to develop targeted chemotherapy strategies that are based on selective expression of receptors in tumor vasculature.
Arap
W
W
Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
Pasqualini
R
R
Ruoslahti
E
E
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D001435:Bacteriophages; D003331:Coronary Vessels / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D004337:Drug Carriers; D006321:Heart / Q000187:drug effects; D006801:Humans; D039564:Integrin alphaV; D016023:Integrins / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000098:blood supply* / Q000188:drug therapy* / Q000473:pathology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000378:metabolism / Q000627:therapeutic use / Q000633:toxicity; D019151:Peptide Library; D011897:Random Allocation; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000970:Antineoplastic Agents; D004337:Drug Carriers; D039564:Integrin alphaV; D016023:Integrins; D009842:Oligopeptides; D019151:Peptide Library; C109962:doxorubicin cysteinyl-asparagyl-glycyl-arginyl-cysteine conjugate; C109961:doxorubucin cysteinyl-aspartyl-cysteinyl-arginyl-glycyl-aspartyl-cycsteinyl-phenylalanyl-cysteine conjugate; D004317:Doxorubicin