Journal
CANCER CELL
Volume 16, Issue 6, Pages 510-520Publisher
CELL PRESS
DOI: 10.1016/j.ccr.2009.10.013
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Funding
- National Cancer Institute [CA104898, CA115410, CA119414, CA119335, CA30199]
- Department of Defense [W81XWH-08-1-0727, W81XWH-08-BCRP-CIA]
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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 alpha v 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.
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