1. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk MRI GUIDED FOCUSED ULTRASOUND ACTIVATED NANO ENCAPSULATED TARGETED DRUG DELIVERY Doudou Xu PhD Student Institute for Medical Science and Technology (IMSaT) University of Dundee, Scotland

2. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Outline Introduction: Nanoporation Project Thermal Sensitive Sugar Based Carrier Nano-Sonication Conclusion Future Study

3. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Nanoporation Nanoporation is an interdisciplinary project Pre-clinical oncology research Cell biology Magnetic Resonance guided Focused Ultrasound Surgery((MRgFUS) Drug encapsulation nano-capsules Targeted delivery of existing chemotherapy drugs Nano-scale sonication research

4. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk MRgFUS- Magnetic Resonance guided Focused Ultrasound Surgery MRgFUS combines High Intensity Focused Ultrasound, that ablates a targeted tissue (non-invasively) monitored by MRI HIFU treated turkey breast

5. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk The Nano-vehicles Sugar based nanocarrier which can increase the solubility of hydrophobic drugs The encapsulation is at molecular level The carrier is triggered to release the drug at the tumor site Peptide Carrier Encapsulated drug Targeting group

6. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Thermo-Sensitive Carrier (I)  = I [carrier]0 -I [carrier]x Encapsulation percentage around 95%; 40-fold more uptake at 80°C than 37°C for Doxorubicin encapsulated carrier solution;

7. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Thermo-Sensitive Carrier (II) Hyperthermia increased penetration of Doxorubicin Hyperthermia decreased binding constant and release Doxorubicin No Thermal EffectThermal Effect Hyperthermia Release Drug Carrier

8. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk In vitro Sonication Machine (I)

9. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk In vitro Sonication Machine (II)

10. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Nano-Sonication Doxorubicin Uptake Test Excitation λ =485nm Emission λ =592.05nm Slit=10 592.05nm With US (23.42) No US (11.79) Fluorescence Digraph

11. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Conclusion Optimised carrier for Doxorubicin encapsulation efficiency is over 95% CapsuTech sugar based carrier is sensitive to thermal effect Hyperthermia mediated by sonication has been validated

12. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Future Studies In vitro Viability test of Nano-Sonication by encapsulated Doxorubicin In vivo studies in mice using ExAblate to release Doxorubicin from Nano-Carrier. Encapsulation of additional drugs (Taxol, Camptothecin, and more) Polymer level encapsulation research

13. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Capsutech, Ltd, Israel: Jallal Gnaim, PhD, CTO-Founder Fabian Arditti, PhD, R&D Manager, Dana Gurevich, PhD student. Doudou Xu, PhD student Nizar Mishael, CPO, Bus. Dev. Insightec, Ltd, Israel: Yoav Medan, D.Sc., Chief System Architect Alex Volovick, M.Sc, Scientist Osnat Dogadkin, M.Sc. Scientist Bjoern Gerold, PhD Student. Yelena Vachutinsky, PhD, scientist Institute for Medical Science and Technology (IMSAT), and University of Dundee, UK: Prof. Andreas Melzer, MD, Director of IMSaT Prof. Sandy Cochran, PhD, Deputy Director Lijun Wang, PhD, Head of Biol.Lab Paul Prentice, PhD, Scientist Ritu Maliki, PhD, Post-Doc Our Team:

14. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk Acknowledgement This research, Nanoporation, is an FP7 funded Marie Curie Industry-Academia Partnerships Pathway project, my studies are currently fully supported by Nanoporation Supervisors in University of Dundee: Prof. Andreas Melzer, Dr. Lijun Wang Supervisors in CapsuTech: Dr. Jallal Gnaim, Dr. Fabian Arditti

15. The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013) under Grant Agreement no 230674 SMIT 14.Sep.2011 Doudou Xu d.z.xu@dundee.ac.uk