Nanomedicine, or translational nanotechnology to improve human health, represents the most direct and dynamic interface to date between the power of the physical sciences and the complexities of biology. The field provides an unparalleled opportunity for multidisciplinary research. It is only by linking the highly quantitative abilities and approaches of chemists, pharmaceutical scientists, biologists, engineers, computer scientists and physicians to the complex knowledge and insights of biologists and clinicians, that the biomedical research field will prosper. Much of the current excitement in the field relates to potential applications such as improved delivery of drugs, enhanced imaging capabilities and more sophisticated diagnostic tools. UNC has created a strong foundation for biomedical research based on multidisciplinary research, industrial partnerships (e.g., linkages to Research Triangle Park), and training. As will be highlighted throughout this proposal, UNC has identified and developed nanotechnology as a strategic focus area. The Small Times recently ranked UNC-Chapel Hill fifth in the United States in university-based nanotechnology research (behind Penn State, Washington, Maryland, and Cornell) (April 29, 2009).
Biophysical Transport of Nanoparticles and Biointeractions
The elucidation of the biophysical transport mechanisms of nano-based delivery systems is at the heart of a successful research program in translational nanotechnology. The potential of nanotechnology to improve human health may be fully realized when aspects of transport (epithelial, endothelial, and cellular) are better understood along with how the physical/chemical characteristics of nanoparticles influence their stability, biodistribution, and toxicology. The premise of this general area of study is that the knowledge obtained may facilitate nano-based therapeutics and imaging discoveries for applications across a wide spectrum of problems in the biomedical research field.
- Epithelial membrane transport: Transport across mucosal epithelial membranes comprise the fundamental route by which pathogens enter the body. Knowledge obtained in this area can, for example, provide new opportunities for protective mucosal vaccine delivery systems, pulmonary nanomedicines, and enhanced oral delivery of macromolecular drugs.
- Vascular (blood) distribution and pharmacokinetics (PK): Opsonization remains an obstacle for nanoparticles gaining access to the blood or injected directly into the vascular compartment. These events may result in facilitated uptake by the Reticuloendothelial System (RES), or neutralization of ligand-mediated delivery. In addition, interaction of nanoparticles with blood cells (platelets, RBCs, WBCs) within the first moments after injection may dictate PK and distribution of the nanoparticles.
- Endothelial membrane transport: The enhanced permeation and retention effect (EPR) has long been exploited with partial success to deliver drugs and nanoparticles more effectively to solid tumors. Understanding the transport (convection) of nanoparticles to and across endothelial membranes and through interstitial space may allow for new therapeutic opportunities in targeting therapeutics to tumors, the liver, and the brain, among others.
- Target cell membrane interaction and intracellular localization and trafficking: New molecular-based therapies including siRNA and gene therapy require effective cellular delivery. There is a continuing need to understand the factors (physical/chemical/biological) that influence nano/cell interactions, endocytotic pathways, endosomal escape mechanisms, and sub-cellular localization (mitochondrial, cytosolic, nuclear, etc.). There also remains a related need to merge ligand discovery efforts (i.e., aptamers, DARPins, peptides, antibodies, etc.) with nano-based delivery systems to fully realize the potential of targeted and safe therapeutics.