MULTIFUNCTIONAL EGFR TARGETING NANOVEHICLES FOR THE TREATMENT OF BRAIN TUMORS
Led by Rolf Barth, MD at Ohio State University
Our proposal describes a highly innovative approach for specifically targeting a brain tumor associated molecular target, the epidermal growth factor receptor (EGFR), with multifunctional therapeutic and diagnostic delivery agents called “nanovehicles” (NVs). These will incorporate the anti-cancer drug, cisplatin, and a tracer that will allow these NVs to be tracked by a special type of imaging following their administration. The bloodbrain barrier severely limits the amount of drug that can reach the brain tumor. This can be circumvented by administering the drug directly into the brain using a special technique called convection enhanced delivery (CED). Basically, a small syringe pump applies pressure to delivery the drug to the site of the brain tumor. By administering these NVs directly into the brain by CED, we will completely eliminate the problems that occur when the drugs are administered intravenously. Furthermore, by including the tracer in the NVs it will be possible to follow their distribution by means of imaging. The advantage of using targeted NVs is that they provide more specific tumor targeting with larger amounts of the drug and eliminate toxicity to the rest of the body. The targeting agent that we will use is an antibody that recognizes EGFR. The cisplatin will be linked to a carrier, somewhat like a freight train since it can carry a large amount of the drug. This will be chemically linked
to the antibody. Since cisplatin and the anti-EGFR antibodies kill tumors by totally different mechanisms, this will enhance tumor cell killing. Furthermore, combining these NVs and X-ray treatment will enhance their killing effect. If we can demonstrate that these NVs are both safe and effective when administered to brain tumor bearing rats, this could pave the way to develop a clinical trial to treat patients with brain tumors.
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