ABSTRACT
The confirmation in several model systems of the αvß3-dependent anti-angiogenic properties of Nanotetrac and the proliferative action of thyroid hormone on multiple cancer cell lines caused us to examine Nanotetrac and tetrac for anti-cancer cell properties that originate at the integrin. The nanoparticulate formulation involved a stable ether bond of the outer ring of tetrac to a diaminopropane linker and amide-bonding of the latter to poly(lactic-co-glycolic acid). The amide bond was imbedded in the nanoparticle and thus not readily accessible to circulating or tissue peptidases. Studied in vitro in human retinal endothelial cells, Nanotetrac and tetrac inhibited the pro-angiogenic activity of Vascular endothelial growth factor and erythropoietin. The hemoglobin content of xenografts of cancer cells is an index of tumor vascularity/angiogenesis. Exposed in situ to systemically administered Nanotetrac, these xenografts have regularly exhibited a decrease of 50% or more in hemoglobin content.
