DEVELOPMENT OF A CELL-BASED NANOFORMULATED ANTI-TUMOR THERAPY

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The use of Cell-based drug delivery systems that target disease sites may revolutionize the health care industry. Such cell-based-drug-formulations are in their infancy but have shown "proof of concept". Drugs that are absorbed onto a particle surface and entrapped inside a cell can be dissolved within a particle matrix. Cell-based nanoformulated drug delivery system like those developed herein may be used for treatments and diagnosis of a broad range of diseases including cancer and neurodegenerative disorders. The proposal will develop nanoformulations that can be packaged into macrophages and be delivered to brain tumor sites in laboratory and animal models of human disease. The basis of our drug delivery system is bone marrow or monocyte-derived macrophages (BMM and MDM). These cells will be used as drug carriers. As neuroinflammatory responses are induced by brain tumors including the development of a chemokine gradient, this biological response leads to monocyte-macrophage attraction to diseased brain regions. We posit that BMM or MDM recruited into areas of brain disease can improve therapeutic outcomes by enhancing brain penetrance and/or efficacy. Importantly, our cell-based delivery can improve misdistribution and reduce chemotherapy-induced neurotoxicity. The foundation on which this project is built are recently developed animal model systems that monitor the biologic, immune and physiologic effects of primary human brain tumors. We will utilize an infrastructure of our Nebraska Center for Nanomedicine (NCN) to develop integrated imaging, pathology, and tumor biology platforms to investigate how anti-tumor therapies delivered in cells may be optimally utilized in treatments for malignant brain tumors. The project is designed to test divergent nanoformulations in both laboratory and animal model studies and takes full advantage of the core structures within the NCN. All together, the studies should permit a better understanding of how anti-neoplastic drugs can be effectively most effectively to improve disease outcomes.