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“ Bionano ” research lines

“ Bionano ” research lines. Prof. Nicola Rosato Dr. Massimo Bottini. “Bionano” research lines. Summary. Nanotechnology, nanodrugs and carbon nanotubes “Bionano” research lines: the past “Bionano” research lines: the present

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“ Bionano ” research lines

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  1. “Bionano” research lines Prof. Nicola Rosato Dr. Massimo Bottini

  2. “Bionano” research lines Summary Nanotechnology, nanodrugs and carbon nanotubes “Bionano” research lines: the past “Bionano” research lines: the present “Bionano” research lines: nanodrugs for intratumor Treg targeting “Bionano” research lines: the future Conclusions Acknowledgments NAST Workshop, July 3, 2013, Rome

  3. “Bionano” research lines Nanotechnology, nanodrugs and carbon nanotubes 1. NAST Workshop, July 3, 2013, Rome

  4. “Bionano” research lines Nanotechnology The science of manipulating matter at the atomic and molecular level to obtain materials with specifically enhanced chemical and physical properties. Energy Information Technology • More efficient and cost effective technologies for energy production • Solar cells • Fuel cells • Batteries • Bio fuels • Smaller, faster, more energy efficient and powerful computing and other IT-based systems Consumer Goods • Foods and beverages • Advanced packaging materials, sensors, and lab-on-chips for food quality testing • Appliances and textiles • Stain proof, water proof and wrinkle free textiles • Household and cosmetics • Self-cleaning and scratch free products, paints, and better cosmetics Medicine • Cancer treatment • Bone treatment • Drug delivery • Appetite control • Drug development • Medical tools • Diagnostic tests • Imaging NAST Workshop, July 3, 2013, Rome

  5. “Bionano” research lines Nanodrugs NAST Workshop, July 3, 2013, Rome

  6. “Bionano” research lines Single-walled carbon nanotubes (SWCNTs) NAST Workshop, July 3, 2013, Rome

  7. “Bionano” research lines “Bionano” research lines: the past 2. NAST Workshop, July 3, 2013, Rome

  8. “Bionano” research lines Chemically-modified nanoparticles NAST Workshop, July 3, 2013, Rome

  9. “Bionano” research lines Chemically-modified nanoparticles NAST Workshop, July 3, 2013, Rome

  10. “Bionano” research lines PEG-modified carbon nanotubes in bio-medicine NAST Workshop, July 3, 2013, Rome

  11. “Bionano” research lines “Bionano” research lines: the present 3. NAST Workshop, July 3, 2013, Rome

  12. “Bionano” research lines Present projects Protein corona of PEG-modified carbon nanotubes Biodegradation of PEG-modified carbon nanotubes NAST Workshop, July 3, 2013, Rome

  13. “Bionano” research lines Present projects Biocompatibility of PEG-modified carbon nanotubes IntratumorTreg targeting by PEG-modified carbon nanotubes NAST Workshop, July 3, 2013, Rome

  14. “Bionano” research lines Nanodrugs for intratumorTregtargeting 4. NAST Workshop, July 3, 2013, Rome

  15. “Bionano” research lines Spleen (tumor) Tumor Spleen (healthy) Background: Treg in tumor development CD4+CD25highFoxP3+ regulatory T cells (Treg) are harnessed by tumors to protect themselves from host anti-tumor responses. Immune cell relative abundance NAST Workshop, July 3, 2013, Rome

  16. “Bionano” research lines Background: Treg in tumor development The manipulation of Treg function selectively into tumors might be the next frontier of cancer immunotherapy. RES PEG-modified carbon nanotubes Tumor CD4 = carbon nanotube TCR/CD3 = monoclonal antibody = PEG CD25 = fluorochrome Regulatory T cell = cargo NAST Workshop, July 3, 2013, Rome

  17. “Bionano” research lines = SWCNT = PEG = fluorochrome = targeting agent = Treg-specific receptor PEG-SWCNTs for intratumorTreg targeting 10141 nm Spleen Tumor NAST Workshop, July 3, 2013, Rome

  18. “Bionano” research lines Choosing the target marker GITR FR4 CD39 CD103 Spleen (healthy) Spleen (tumor) Tumor NAST Workshop, July 3, 2013, Rome

  19. “Bionano” research lines * * * * * * * * * * * * * * * * * * * * * * * Ex vivo PEG-SWCNT-DTA1 Treg targeting efficiency and selectivity Effect of number of DTA-1 mAb/SWCNT Effect of incubation time Effect of dose * NAST Workshop, July 3, 2013, Rome

  20. “Bionano” research lines Ex vivo PEG-SWCNT-DTA1 trafficking 1 hour 1 hour + 5 hours 6 hours NAST Workshop, July 3, 2013, Rome

  21. “Bionano” research lines * * * * * * * * * * * * Ex vivo PEG-SWCNT Treg targeting efficiency and selectivity Anti-FR4 mAb Anti-CD39 mAb Anti-CD103 mAb * * * * NAST Workshop, July 3, 2013, Rome

  22. “Bionano” research lines * * * * * * Ex vivo PEG-SWCNT Treg targeting efficiency and selectivity Treg targeting efficiency vs. receptor Treg targeting selectivity vs. receptor Tregvs. Teff Tregvs. Unstained NAST Workshop, July 3, 2013, Rome

  23. “Bionano” research lines * * * In vivo studies Targeting efficiency (spleen of healthy mice) Targeting efficiency (B16-bearing mice) Pharmacokinetic profile NAST Workshop, July 3, 2013, Rome

  24. “Bionano” research lines “Bionano” research lines: the future 5. NAST Workshop, July 3, 2013, Rome

  25. “Bionano” research lines Nanodrugs for Treg-specific cancer immunotherapies Aim 1. Assess tumor killing elicited by PNT-DTA1. We will assess attenuation of intra-tumor Treg function and efficient tumor-killing by PNT-DTA1 systemically administered to B16-bearing mice. Aim 2. Assess increased intra-tumor delivery of PNT-DTA1 elicited by co-administered iRGD peptides. We will assess whether co-administration of PNT-DTA1 with iRGD peptides leads to a tumor-specific increase in nanoparticle accumulation and Treg targeting, and more efficient tumor killing in B16-bearing mice. NAST Workshop, July 3, 2013, Rome

  26. “Bionano” research lines Nanodrugs for RA 2,5ug 5ug 10ug NAST Workshop, July 3, 2013, Rome

  27. “Bionano” research lines Conclusions  Treg-targeting efficiency and selectivity of PEG-SWCNT-DTA1 depend on number of ligands per nanotube, incubation time, dose, and targeted surface marker.  PEG-SWCNT-DTA were internalized by Treg through receptor-mediated endocytosis and transported into the cytoplasm and nucleus ex vivo and in vivo.  Injection of PEG-SWCNT-DTA1 in animals carrying tumors enabled very good targeting of Treg residing in the tumor microenvironment, while much less efficiency and almost no selectivity was evident in the spleen. Preferential penetration of nanoparticles into the tumor microenvironment compared to other tissues (i.e. spleen) was a consequence of EPR effect naturally increased intra-tumor Tregvs.Teff ratio use of markers that are enriched in intra-tumor vs. peripheral Treg(i.e. GITR)   PEG-SWCNTs were degraded by activated neutrophils in approximately 3 hours NAST Workshop, July 3, 2013, Rome

  28. “Bionano” research lines Acknowledgements Massimo Cristiano Novella The Prof. Prof. N. Bottini’s Lab Prof. A. Magrini Prof. M. Mattei Dr. A. Pietroiusti Dr. L. Campagnolo Prof. E. Ruoslahti Prof. B. Fadeel Arthritis National Research Foundation Prof. A. Star NAST Workshop, July 3, 2013, Rome

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