A Novel Multiple Ligand Approach to Targeting Tumors

Georgia Tech Research Corporation, Atlanta GA

Investigators

Abstract

0201891 Bellamkonda Inability to successfully target chemotherapeutic agents to tumors, specifically gliomas of the brain, has been a major obstacle for successful treatment and prognosis. While liposomal delivery to gliomas has been promising, non-specific delivery of chemotherapeutic agent(s) remains high. The investigators propose a novel, multiple-ligand approach to target drug-laden liposomes to brain tumors in an efficient manner while minimizing non-specific uptake at the same time. The approach is based on the following hypotheses: A) The overall affinity between receptor targeted drug delivery vehicle and tumors can be increased by using multiple weak interactions generated by multiple targeting ligands on the delivery vehicle that target multiple differentially (but not exclusively) expressed receptors on tumors, and B) Specificity of targeting can be achieved by delivery vehicles presenting sub-optimal levels of each ligand (with optimal being maximum possible affinity for a given ligand), so that non-specific uptake by healthy cells is reduced because they do not coincidently over-express all of the targeted receptors that are differentially expressed on gliomas. Based on these hypotheses, the specific aims are to: 1) Design and fabricate multiple-ligand presenting liposomal vehicles; 2) Determine doxorubicin loaded multiple ligand vehicles' targeting capacity when tumor and non-tumor cells are co-cultured; and 3) Determine the in vivo performance of these vehicles in a rodent model of glioma.