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Probes Encapsulated by Biologically-Localized Embedding

Probes Encapsulated by Biologically-Localized Embedding. Probes Encapsulated by Biologically-Localized Embedding. Probes Encapsulated by Biologically-Localized Embedding. Martin A. Philbert, Professor of Toxicology The University of Michigan. Neurotoxicology & Experimental Neuropathology:

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Probes Encapsulated by Biologically-Localized Embedding

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  1. Probes Encapsulated by Biologically-Localized Embedding Probes Encapsulated by Biologically-Localized Embedding Probes Encapsulated by Biologically-Localized Embedding Martin A. Philbert, Professor of Toxicology The University of Michigan Neurotoxicology & Experimental Neuropathology: Dr. Murphy Brasuel Dr. Hao Xu Amanda Phelka James Miller Randy J. Schneider III Stephanie Runkle Rhonda Lightle Sevanne Demerijian Dr. Terry Miller Prof. Ron Tjalkens Dr. Marion Hoyer Chemistry, Physics and Applied Physics: Prof. Raoul Kopelman Jeff Anker Caleb Behrend James Sumner Ed Park Dr. Maria Moreno Matt King Dr. Yong-Eun Koo Prof. Jon Aylott Dr. Eric Monson Dr. Steve Parus Dr. Heather Clark

  2. Probes Encapsulated by Biologically-Localized Embedding The University of Michigan Engineering: Prof. Ann Marie Sastry Stochastic modeling and percolation theory Prof. Christian Lastoskie Atomistic/Molecular modleling Dr. Chia-Wei Wang Dr. Hui Zhu Dr. Yun Bo Mr.Brad Layton Radiology/ Radiation Oncology & MRx Prof. Al. Rehemtulla Prof. Brian Ross MR-Imaging and Targeting MRx Prasad Sunkara CEO Dr. Ram Reddy Dr. Brad Moffat Dr. Nandanan Erathodiyil

  3. DARPA NCI NIEHS NIGMS The W.M. Keck Foundation Unconventional Pathogen Countermeasures Unconventional Innovations Program 1R01-ES08846 (MAP) R01 (RK) Modeling of Intracellular Transport Processes Grant Support

  4. Application of Nanotechnology to Environmental Health Sciences Best solution to problems in environmental health sciences will likely involve hybrid nanotechnologies Sensors and actuators in the same very small device Therefore, assessments of individual components may not be helpful i.e., the way nanoparticles are assembled may not be the way they disassemble

  5. Fantastic Voyage: From Nano-Explorers to Nano-Doctors Issac Asimov (1966)

  6. PEBBLES (Probes Encapsulated By Biologically Localized Embedding) 20 nm - 600 nm in diameter Note: 20 nm PEBBLE = <1 ppb of 50 mm Human motor neuron • Protects Dye from Cellular Artifacts • Protects Cellular Environment from Dye Toxicity

  7. Currently Available Matrices Hydrophobic Plasticized PVC Polydecylmethacrylate Hydrophilic Polyacrylamide – hydrogel Amphiphilic Sol-gel Ormasil

  8. DNP Surface Modification & Targeting CURRENTLY: HIV-TAT peptide nuclear targeting Phi-OX in vitro cancer expts Cyclized RGD in vivo targeting of microvasculature Mutant Il-13 in vivo high grade gliomas

  9. Confirmation of Intracellular Placement TEM images of PEBBLE sensors shot into neuroblastoma cells using gene gun bombardment

  10. Sensor Preparation • Polymer matrix & synthesis techniques. • Decyl methacrylate, Silica, or polyacrylamide • Microemulsion, Sol-gel, or Stöber method

  11. 0.6 0.5 0.4 Differential Number Fraction 0.3 0.2 0.1 0 92.5 97.5 102.5 Hydrodynamic Radius (nm) Size & Morphology • Multi angle light scattering (50-800nm) • TEM images show gold nanoparticles outside or inside depending on preparation method. 100 nm

  12. Gene Gun Schematic Liposomal Delivery

  13. Real-Time 3-D Confocal PEBBLE imaging

  14. Ratiometric Calcium PEBBLEs Confocal microscope image of C6 glioma cells containing Calcium Green/sulfarhodamine PEBBLEs (toxin moving left to right).

  15. Ratiometric PEBBLE

  16. COMPLEXITY HELPS: Liquid Polymer PEBBLE 20 nm – 600 nm in diameter

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