Project 1 - Nanomaterials: From discovery to translation
Project Leader - Karen L. Wooley, Ph.D.
The primary goals of this Project are the discovery of new nanotechnology platforms for integration into the clinical applications of the other Projects and, ultimately, translation.
We have made significant progress on the design and development of unique and well-defined, multi-functional nanostructures during the five years of our initial PEN grant. A wide spectrum of nanomaterials was initially examined (multiple variations on > 8 distinct classes of nanomaterials), from which select structures were identified and further optimized for antimicrobial delivery in treating lung infectious diseases, gene imaging and regulation in diagnosing and treating acute lung injury, and imaging and treating acute vascular injury and atherosclerosis. All of our NPs are derived from robust, efficient and controlled polymer chemistries, and each has properties that have been determined through an iterative and multi-disciplinary series of investigations that have led uniquely to their selection for further development of their clinical application in vivo. Such platform development and translation work will be performed in Projects 2-4 and the Developmental Projects, with support by Project 1 and the Nanomaterials Production Core for continued improvements in performance. In addition, Project 1 will build on our previous work with the development of a focused array of vastly enhanced nanomaterials having the level of performance and scalability necessary for translation.
The developmental specific aims include:
The discovery specific aims include:
- Optimize the best of our existing nanomaterials for degradability, scalability and translation for an eventual IND submission and clinical trials;
- Optimize targeting ligand and nanomaterial carrier for polyvalent presentation to achieve highest (pM) binding affinity and specificity to biological receptors.
- Design responsive, transformative nanostructures for targeted therapeutic delivery;
- Construct hierarchically-assembled, multi-functional nanoscale objects, capable of combining distinctive targeting, imaging and therapy sub-units in a modular manner;
- Demonstrate unique triggering mechanisms for milieu-selective therapeutic release.
Each aim will be completed with focus upon a specific disease target, to provide for significant fundamental and translational advances of these nanotechnologies. General advances will be realized that will result in broad applicability of these nanomaterial platforms, beyond the specific systems proposed.