title: Tissue-penetrating delivery of compounds and nanoparticles into tumors.
abstract: Poor penetration of drugs into tumors is a major obstacle in tumor treatment. We describe a strategy for peptide-mediated delivery of compounds deep into the tumor parenchyma that uses a tumor-homing peptide, iRGD (CRGDK/RGPD/EC). Intravenously injected compounds coupled to iRGD bound to tumor vessels and spread into the extravascular tumor parenchyma, whereas conventional RGD peptides only delivered the cargo to the blood vessels. iRGD homes to tumors through a three-step process: the RGD motif mediates binding to alphav integrins on tumor endothelium and a proteolytic cleavage then exposes a binding motif for neuropilin-1, which mediates penetration into tissue and cells. Conjugation to iRGD significantly improved the sensitivity of tumor-imaging agents and enhanced the activity of an antitumor drug.
authors: Vascular Mapping Center, Burnham Institute for Medical Research at UCSB, Biology II Building, University of California, Santa Barbara, Santa Barbara, CA 93106-9610, USA.
authors: Kazuki N
authors: KN
authors: Sugahara
authors: Tambet
authors: T
authors: Teesalu
authors: Priya Prakash
authors: PP
authors: Karmali
authors: Venkata Ramana
authors: VR
authors: Kotamraju
authors: Lilach
authors: L
authors: Agemy
authors: Olivier M
authors: OM
authors: Girard
authors: Douglas
authors: D
authors: Hanahan
authors: Robert F
authors: RF
authors: Mattrey
authors: Erkki
authors: E
authors: Ruoslahti
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D016023:Integrins / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D053758:Nanoparticles; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009374:Neoplasms, Experimental / Q000378:metabolism* / Q000473:pathology; D039942:Neuropilin-1 / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D016023:Integrins; D009842:Oligopeptides; D039942:Neuropilin-1; C047981:arginyl-glycyl-aspartic acid