Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels

Dennis Hallahan, Ling Geng, Shimian Qu, Christopher Scarfone, Todd Giorgio, Edwin Donnelly, Xiang Gao, Jeff Clanton

Research output: Contribution to journalArticle

114 Scopus citations

Abstract

The objective of this study was to target drug delivery to radiation-induced neoantigens, which include activated receptors within the tumor vasculature. These responses include posttranslational changes in pre-existing proteins, which can be discovered by phage-displayed peptide libraries administered to mice bearing irradiated tumors. Phage-displayed peptides recovered from irradiated tumors included the amino acid sequence RGDGSSV. This peptide binds to integrins within the tumor microvasculature. Immunohistochemical staining of irradiated tumors showed accumulation of fibrinogen receptor α2bβ3 integrin. We studied tumor targeting efficiency of ligands to radiation-induced α 2bβ3. Radiopharmaceuticals were localized to irradiated tumors by use of α2bβ3 ligands conjugated to nanoparticles and liposomes. Fibrinogen-conjugated nanoparticles bind to the radiation-activated receptor, obliterate tumor blood flow, and significantly increase regression and growth delay in irradiated tumors. Radiation-guided drug delivery to tumor blood vessels is a novel paradigm for targeted drug delivery.

Original languageEnglish
Pages (from-to)63-74
Number of pages12
JournalCancer Cell
Volume3
Issue number1
DOIs
StatePublished - Jan 2003
Externally publishedYes

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    Hallahan, D., Geng, L., Qu, S., Scarfone, C., Giorgio, T., Donnelly, E., Gao, X., & Clanton, J. (2003). Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels. Cancer Cell, 3(1), 63-74. https://doi.org/10.1016/S1535-6108(02)00238-6