AGFD 52 |
| The central focus of our research is to endow drug carriers a switching function to surface properties, drug release rate (slow/fast) and surface ligand exposure (hidden/exposed). The switching function utilizes internal signals rather than external external ones, namely the slightly acidic extracellular pH or early endosomal pH. Acidic extra cellular pH is a consistent and intrinsic property of solid tumors. The switching function in our carriers is believed to induce the least side effects for chemotherapy by minimizing drug release rate and cellular or organ uptake during circulation. When the carriers reach the tumor sites by EPR mechanism, the drug release is accelerated, the cellular interactions are enhanced for active internalization, and a specific ligand, antibody or receptor is exposed for receptor-mediated endocytosis for maximum therapeutic efficacy. The exposure of ligands only at tumor sites will enable one to use even tumor non-specific ligands, thus expanding the battery of tumor targeting tools. A reduced immune response of a specific antibody employed for targeting is also anticipated by adopting such switching mechanisms. Targeting early endosomal pH with endosomolytic function is a critical factor in designing polymeric gene vectors for practical application in in vivo models, clinical settings and anticancer drug carriers which can bypass one of the major defense mechanisms of multidrug resistance tumors (sequestration and exocytosis). Carriers equipped with active internalization tools, endosomolytic function and loaded with a Pgp substrate drug do not distinguish wild-type and resistant tumors. The cell killing rate in in vitro as well as in vivo experiments is similar for both tumors. |
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Advances in Biobased Nanostructures and Nanomaterials
1:30 PM-4:55 PM, Monday, August 20, 2007 BCEC -- 255, Oral
Division of Agricultural & Food Chemistry |