1. Defining the right clinical problems for nanotechnology Table 2 John S. Oghalai, MD

2. Potential Clinical Goals of Nanotechnology

3. 1. Nanotechnology to change the surface of implanted devices Premise: on the nanoscale, adhesion properties of surfaces may be different –To decrease biofilm formation of pathogenic organisms –To increase the ability of beneficial organisms to form biofilms Examples: vascular stents, indwelling catheters, cochlear implants, pacemakers

4. 2. Mechanical modulation of biologic components Premise: carbon nanotubes are stiff and may cross-link collagen fibers Examples –To stiffen the eardrum for the treatment of cholesteatoma or atelectasis –To stiffen the basilar membrane within the cochlea and alter the frequency sensitivity of hearing –To stiffen the skin in patients with chronic skin disorders and ulcerations –Tendon and/or bone strengthening

5. 3. Topical Gene Therapy Premise: carbon nanotubes can be used to transport exogenous DNA into a cell and could be applied locally with minimal risk Examples of potential use for gene delivery: –To the cochlea for the treatment of hearing loss –To the eye for visual loss –To the skin –To blood vessels, via endovascular application

6. 4. Neural Regeneration & Repair Premise: Nanotubes conduct electricity and can be fabricated in parallel matrices Examples: –To repair the facial nerve after planned surgical sacrifice –To repair the spinal cord after traumatic injury –To repair or restore function in long nerves to extremities in diabetics or other patients with peripheral nerve disease

7. 5. Drug delivery Premise: Nanotubes can transport drugs Examples: –Deliver alpha radiation to cancer micrometastases –Deliver compounds to areas of vascular stenosis or occlusion (heart, brain, etc.) –Deliver growth factors to chronic wounds –Deliver substances across the blood-brain and blood- perilymph (inner ear) barriers –Delivery of anti-HIV therapies to T-cells

8. 6. Imaging Premise: Nanotubes can carry contrast agents Examples: –Transportation of gadolinium to improve MRI sensitivity

9. Barriers to developments in these areas

10. Technical barriers Toxicities of nanomaterials are unknown How to best target the nanomaterials so that systemic administration can be used How to uncage the drug so it gets out at the desired location Is there a way to “re-cage” the drug when it is no longer desired How are nanoparticles removed from the body Mathematical modeling of nanostructures is in its infancy

11. Other barriers Identifying potential collaborators between institutions, departments, and backgrounds Obtaining seed grant funds to start novel projects Obtaining large amounts of funding to be able tp translate successful results from animal studies into clinical phase 1 trials.

12. Opportunities for the Texas Medical Center

13. Action Items Make the Collaborative Research Center (CRC) the hub for nanomedicine interactions Weekly or bi-weekly seminar series dedicated to nanotechnology research Increase number of Rice graduate students and post-docs working in collaborations with biological labs within the Texas Medical Center