Integrins are membrane-spanning heterodimers that mediate cell-extracellular matrix adhesion. Cyclo(-RGDfK) Trifluoroacetate is a potent and selective inhibitor of purified αvβ3 integrin with a KD value of 41.70 nM. In HEK293 (β3) cells, incubation with 2 μM Cyclo(-RGDfK) trifluoroacetate decreased the αvβ3 intergrin lateral mobility compared to the control group. When HEK293 (β3) cells were starved for 30 min and incubated with 1 μM Cyclo(-RGDfK) trifluoroacetate-Cy5 for 10 min at room temperature, the αvβ3 integrin internalization was less extensive than that in cells treated with regioselectively addressable functionalized template-arginine-alanine-aspartic acid (RAFT-RGD). Additionally, the internalization of αvβ3 integrin in HEK293 (β3) was dose-dependently induced by RAFT-RGD, and reached 79% increase versus control group at the dose of 1 μM. On the contrary, increasing doses of cyclo(-RGDfK) trifluoroacetate (0.1 - 4 μM) did not affect the integrin internalization as compared to the control cells[3]. In athymic mice bearing αvβ3-integrin-positive C6 gliomas, administration of cyclo(-RGDfK) trifluoroacetate conjugated to 177Lu-gold nanoparticles (2MBq/0.05 mL, four times from day 1 to 21) suppressed tumor progression, tumor metabolic activity, the number of intratumoral vessels and VEGF gene expression compared to mice treated with other radiopharmaceuticals[4].
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