TY - JOUR
T1 - Integrin-mediated targeting of drug delivery to irradiated tumor blood vessels
AU - Hallahan, Dennis
AU - Geng, Ling
AU - Qu, Shimian
AU - Scarfone, Christopher
AU - Giorgio, Todd
AU - Donnelly, Edwin
AU - Gao, Xiang
AU - Clanton, Jeff
N1 - Funding Information:
We thank Errki Ruoslahti for peptide phage libraries and Ali Fu, Robert C. Iverson, George Holburn, James Patton, Dawn Shone, Helina Onishko, and Jason Dugger for their technical assistance. This work was supported by NIH grants (R21-CA89888, R01-CA70937, R01-CA58508, P30-CA68485, R01-CA88076, R01-CA89674, and the Vanderbilt Lung Cancer SPORE P50-CA90949), by a training grant from American Society Therapeutic Radiology Oncology, and by developmental funds from the Vanderbilt Department of Radiation Oncology.
PY - 2003/1
Y1 - 2003/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0038162536&partnerID=8YFLogxK
U2 - 10.1016/S1535-6108(02)00238-6
DO - 10.1016/S1535-6108(02)00238-6
M3 - Article
C2 - 12559176
AN - SCOPUS:0038162536
SN - 1535-6108
VL - 3
SP - 63
EP - 74
JO - Cancer Cell
JF - Cancer Cell
IS - 1
ER -