Tissue-Penetrating Delivery of Compounds and Nanoparticles into Tumors

Kazuki N. Sugahara, Tambet Teesalu, Priya Prakash Karmali, Venkata Ramana Kotamraju, Lilach Agemy, Olivier M. Girard, Douglas Hanahan, Robert F. Mattrey, Erkki Ruoslahti

Research output: Contribution to journalArticlepeer-review

916 Scopus citations


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 αv 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.

Original languageEnglish (US)
Pages (from-to)510-520
Number of pages11
JournalCancer Cell
Issue number6
StatePublished - Dec 8 2009



ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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