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Prof. Nicola Rosato Dr. Massimo Bottini. 1.Nanotechnology, nanodrugs and carbon nanotubes 2.Bionano research lines: the past 3.Bionano research lines:

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Presentation on theme: "Prof. Nicola Rosato Dr. Massimo Bottini. 1.Nanotechnology, nanodrugs and carbon nanotubes 2.Bionano research lines: the past 3.Bionano research lines:"— Presentation transcript:

1 Prof. Nicola Rosato Dr. Massimo Bottini

2 1.Nanotechnology, nanodrugs and carbon nanotubes 2.Bionano research lines: the past 3.Bionano research lines: the present 4.Bionano research lines: nanodrugs for intratumor T reg targeting 5.Bionano research lines: the future 6.Conclusions 7.Acknowledgments Bionano research lines 2NAST Workshop, July 3, 2013, Rome

3 3 Bionano research lines

4 The science of manipulating matter at the atomic and molecular level to obtain materials with specifically enhanced chemical and physical properties. Information Technology Energy Medicine Consumer Goods Smaller, faster, more energy efficient and powerful computing and other IT-based systems More efficient and cost effective technologies for energy production Solar cells Fuel cells Batteries Bio fuels 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 Cancer treatment Bone treatment Drug delivery Appetite control Drug development Medical tools Diagnostic tests Imaging 4 Bionano research lines NAST Workshop, July 3, 2013, Rome

5 5 Bionano research lines

6 6 NAST Workshop, July 3, 2013, Rome

7 7 Bionano research lines

8 8 NAST Workshop, July 3, 2013, Rome

9 9 Bionano research lines NAST Workshop, July 3, 2013, Rome

10 10 Bionano research lines NAST Workshop, July 3, 2013, Rome

11 11NAST Workshop, July 3, 2013, Rome Bionano research lines

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

13 13 Bionano research lines NAST Workshop, July 3, 2013, Rome Biocompatibility of PEG-modified carbon nanotubes Intratumor T reg targeting by PEG-modified carbon nanotubes

14 14NAST Workshop, July 3, 2013, Rome Bionano research lines

15 CD4 + CD25 high FoxP3 + regulatory T cells (T reg ) are harnessed by tumors to protect themselves from host anti-tumor responses. 15 Spleen (healthy) Spleen (tumor)Tumor Immune cell relative abundance NAST Workshop, July 3, 2013, Rome Bionano research lines

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

17 17 = SWCNT = PEG = targeting agent = fluorochrome = T reg -specific receptor Spleen Tumor nm Bionano research lines NAST Workshop, July 3, 2013, Rome

18 18 Spleen (healthy) Spleen (tumor) Tumor GITRFR4CD39CD103 Bionano research lines NAST Workshop, July 3, 2013, Rome

19 19 Effect of number of DTA-1 mAb/SWCNT * ** * Effect of doseEffect of incubation time * * * ** * * * * * * * * ** ** * * * Bionano research lines NAST Workshop, July 3, 2013, Rome

20 20 1 hour 1 hour + 5 hours 6 hours NAST Workshop, July 3, 2013, Rome Bionano research lines

21 21 Anti-FR4 mAb * * * Anti-CD39 mAbAnti-CD103 mAb * * * * * * * * ** * * * Bionano research lines NAST Workshop, July 3, 2013, Rome

22 22 * * T reg targeting efficiency vs. receptor * * * * T reg vs. Unstained T reg vs. T eff T reg targeting selectivity vs. receptor NAST Workshop, July 3, 2013, Rome Bionano research lines

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

24 24NAST Workshop, July 3, 2013, Rome Bionano research lines

25 25 Bionano research lines NAST Workshop, July 3, 2013, Rome Aim 1. Assess tumor killing elicited by PNT-DTA1. We will assess attenuation of intra-tumor T reg 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 T reg targeting, and more efficient tumor killing in B16-bearing mice.

26 26 Bionano research lines NAST Workshop, July 3, 2013, Rome 2,5ug 5ug 10ug

27 27 T reg -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 T reg 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 T reg 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 1.EPR effect 2.naturally increased intra-tumor T reg vs. T eff ratio 3.use of markers that are enriched in intra-tumor vs. peripheral T reg (i.e. GITR) Bionano research lines NAST Workshop, July 3, 2013, Rome PEG-SWCNTs were degraded by activated neutrophils in approximately 3 hours

28 Prof. E. Ruoslahti Prof. N. Bottinis Lab Prof. A. Magrini Prof. M. Mattei Dr. A. Pietroiusti Dr. L. Campagnolo NovellaMassimoCristiano Arthritis National Research Foundation 28 Bionano research lines NAST Workshop, July 3, 2013, Rome Prof. B. Fadeel Prof. A. Star The Prof.


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