1. Challenges in Clinical Applications for Nanotechnology N. Tony Eissa, MD Table 3

2. Identifying Clinical Targets Short-term Goal: Take existing mature conventional approach (either diagnostic or therapeutic) and enhance their efficacy using nano technology.

3. Identifying Clinical Targets Diagnosis: Early Detection of Cancer: Use nanoparticles with multiple probes to detect pre-defined changes in specific protein levels in pre-cancerous cells. Imaging for micrometastasis Staging of Cancer

4. Identifying Clinical Targets Therapy: Drug Delivery: Use nanoparticles targeted to specific cancer cell surface receptors to guide delivery Form translational alliance between current biotechnology and nanomedicine

5. Identifying Clinical Targets Some clinical areas amenable to wide use of nanomedicine include Cancer, Diabetes, Thrombosis, Vascular diseases, etc. It is important to emphasize to keep open- mind approach for potential clinical applications.

6. Key Barriers Toxicity: short term - no toxicity in animals long term- not known Toxicity for both the host and the environment should be addressed

7. Key Barriers Conjugation Chemistry Challenges: Making nanoparticles that are application-specific Putting the “drug” on the particle Maintaining drug activity on the particle Making the drug come off the particle once application is done

8. Key Barriers Delivery: Ensuring Delivery to target organ/cell Allow systemic administration but deliver to localized distant sites.

9. Key Barriers “Language” Barriers: between various team involved in nano medicine such as: Chemists Physicists Engineers Mathematicians Molecular cell biologists Clinical Physicians

10. Key Barriers GMP Challenges No standards for: Purity and homogeneity of nanoparticles Manufacturing Methods Testing and Validation

11. Action Items Encourage nano applications to already mature area of research Use nano technology to enhance existing diagnostic or therapeutic applications, e.g., imaging, drug delivery Use established cellular recognition systems for delivery testing

12. Action Items Establish NIH programs and review groups that are “nano-friendly” Fund more toxicological studies for nano applications Increase funding for conjugation chemistry for nano particles

13. Action Items Establish training programs in nano medicine with a focus on interdisciplinary approach Undergraduate T32 graduate and post-graduate K12 program for nano medicine scholars K08, K23 physician scientist programs in nano medicine

14. Action Items GMP NIH and FDA need to discuss with the scientific community standards for GMP and made this information available to investigators rather than leaving the burden of proof to individual investigators