Futures for Medicine from Nanotechnology

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Margery Jacobs
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1 Futures for Medicine from Nanotechnology Regenerative Medicine, Novel Therapies for Cancer, Powerful Diagnostic Tools S.I. Stupp Materials Science, Chemistry, and Medicine Institute for BioNanotechnology in Medicine Northwestern University

2 new teeth Great Targets in Regenerative Medicine reversal and prevention of paralysis or blindness through spinal cord or retina regeneration heart regeneration after infarcts curing Parkinson s and Alzheimer s disease minimizing stroke dysfunction through neuron repair cell therapies for diabetes (only 3,000 pancreas transplants available for 35,000 potential patients) access to new cartilage in adulthood universal repair of all bone fractures

6 self assembled nanofibers AFM PNAS 2002 J. Hartgerink H. Jiang macroscopic gels that can suspend cells in 3D D. Harrington Acta Biomaterialia 2005

7 Bone Cell Surrounded by Nanofibers Biomaterialia 2005

8 nanofibers are formed by a diverse set of molecules can encode multiplexed signals for regenerative targets designed to develop bone cells from stem cells 2 molecules co-assembled JACS 2005

9 Spinal Cord Injury Brain Repair Nature 423, (2003)

10 Sequellae of Spinal Cord Injury glial scar formed by astrocytes axons never observed to grow into lesion

11 Nanofibers Customized for Regeneration in The Central Nervous System Spinal Cord Injury, Parkinson s, Alzheimer s, Stroke, Impaired Vision Non-bioactive Nanofiber Bioactive Nanofiber signals per cm 2 IKVAV epitope known as a neurite sprouting/guiding epitope, present in the extracellular protein laminin Science 2004

12 Neural Stem Cells from embryonic brains 100 μm

13 50 μm

14 in nanofiber network progenitor cells become neurons starting at 24 hours and not astrocytes 50 μm

15 Self-Assembly of a Nanofiber Network at the Site of Spinal Cord Injury Astrocytes Build a Blocking Scar for Axon Regeneration after Injury epitope binds to αβ1 integrins signaling elongates axons and promotes neuron development from stem cells suppresses development of glial cells which generate the blocking and inhibitory scar for axon regeneration

16 Goals Regenerate Bone and Teeth Strategy utilize nanostructures as matrices or nanostructures and stem cells to trigger regeneration of mineralized tissues

17 Some Comments on Bone and Teeth challenges in universal bone repair: genetics, age, disease (cancer), extensive trauma, birth defects the treatment of osteoporotic fractures costs about $14 billion a year in the US 200 million women worldwide have osteoporosis; arthritis, rheumatoid about 1% worldwide 21 natural teeth is the natural marker for functional dentition functional US population: 71.7% aged 20 years and older, 42.4% aged 50 and older

18 flat crystal of bone mineral nucleated on top of nanofiber: mimics the nanoscale structure of bone Nanoscale Structure of Bone Weiner and Wagner QuickTime and a TIFF (Uncompressed) decompressor are needed to see this picture. templated biomineralization sould be an osteogenic signal: many therapies would be possible using these self-assembling and biomineralizing systems

19 Blood Vessels on Demand Needed to Treat Ischemic Disease peripheral vascular disease affects up to 15% of adults over age 55 myocardial infarction 7 million people in the U. S. with history of MI chronic ischemic heart disease leading cause of death in the U.S. and worldwide chronic wound healing (diabetes) U.S.- $2.8 billion annually to treat 3 to 5 million chronic wounds

20 Nanofiber Nucleated by Polysaccharide Promotes Blood Vessel Growth: Activates Angiogenic Proteins the polyion is displayed over high surface area on the nanostructure QuickTime and a TIFF (LZW) decompressor are needed to see this picture. hydrophobic core excludes polyion from the interior NanoLetters 2006

21 blood vessels grow in the cornea within 7 to 10 days collagen matrix control heparin and growth factors growth factors

22 Rapid Blood Vessel Growth Could Save or Regenerate Myocardium after Heart Attacks

24 Nanostructures for Novel Cancer Therapies Co-Assembly and Spatial Organization of Targeting and Therapeutic Agents and Drugs in a Single Nanostructure: dial in quantities of each Externally Triggered Self-Assembly of Lethal Therapies to Cancer Cells in the Interior Compartment of a Delivery Agent: A Liposome

25 Acknowledgements Funding NIH: NIBIB, NCI, NIDCR, NINDS DOE J.A. Kessler J. Lomasney J. Hulvat C. Davidson N. Beohar H. Band V. Band K. Scheidt T. Launey G. Rivera L. Gagne M. Olvera de la Cruz NSF K. Niece K. Rajangam M. Webber S. Soukasene H.K. Lee S. Standley V. Tysseling-Mattiace V. Sahni C. Czeisler G. Silva Y. Velichko S. Sur A. Hung J.L. Calderón T. Paschuk H. Jian J. Hartgerink

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