Overcoming Blood-Brain Barrier By Targeted Drug Delivery To Brain Tumor Vasculature With Carbohydrate Mimetic Peptide In Mouse Glioma Model

Although glioma cells cultured in vitro are responsive to several anti-cancer drugs, it is very difficult to treat glioma in vivo due to blood-brain barrier (BBB). In the previous study, we identified a carbohydrate mimetic peptide, designated as IF7, that homes tumor vasculature. IF7 binds to annexin A1, which is expressed specifically on the endothelial cell surface of malignant tumors. We showed that IF7 conjugated anti-cancer drug SN38 (IF7-SN38) suppressed growth of colon, melanoma, breast, prostate and lung tumor models in the mouse. Since IF7 was thought to be transported across endothelial cells through transcytotic pathway, we hypothesized that IF7 can deliver anti-cancer drug to brain stroma overcoming BBB. In this study, we produced glioma tumors in mouse brains by intracranial injection of C6 cells. To determine targeting of IF7 peptide, Alexa 488-tagged IF7 (IF7-A488) was injected intravenously. IF7-A488 targeted tumor vasculature within minutes, penetrated through endothelial cell wall and s...