MRI GUIDED FOCUSED ULTRASOUND ACTIVATED NANO ENCAPSULATED TARGETED

MRI GUIDED FOCUSED ULTRASOUND ACTIVATED NANO ENCAPSULATED TARGETED DRUG DELIVERY Doudou Xu Ph. D Student Institute for Medical Science and Technology (IMSa. T) University of Dundee, Scotland The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -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 The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

Nanoporation is an interdisciplinary project • Pre-clinical oncology research • Cell biology • Magnetic Resonance guided Focused Ultrasound Surgery((MRg. FUS) • Drug encapsulation nano-capsules • Targeted delivery of existing chemotherapy drugs • Nano-scale sonication research The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

MRg. FUS- Magnetic Resonance guided Focused Ultrasound Surgery • MRg. FUS combines High Intensity Focused Ultrasound, that ablates a targeted tissue (non-invasively) monitored by MRI HIFU treated turkey breast The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -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 Targeting group Encapsulated drug The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

Thermo-Sensitive Carrier (I) • Encapsulation percentage around 95%; • 40 -fold more uptake at 80°C than 37°C for Doxorubicin encapsulated carrier solution; DI=I[carrier]0 -I[carrier]x The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -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 Effect Hyperthermia Release Drug Carrier The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

In vitro Sonication Machine (I) The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

In vitro Sonication Machine (II) The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

Nano-Sonication Doxorubicin Uptake Test Fluorescence Digraph 592. 05 nm With US (23. 42) No US (11. 79) Excitation λ =485 nm The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 Emission λ =592. 05 nm Slit=10 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

Conclusion • Optimised carrier for Doxorubicin encapsulation efficiency is over 95% • Capsu. Tech sugar based carrier is sensitive to thermal effect • Hyperthermia mediated by sonication has been validated The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -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 Ex. Ablate to release Doxorubicin from Nano-Carrier. • Encapsulation of additional drugs (Taxol, Camptothecin, and more) • Polymer level encapsulation research The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

Our Team: Capsutech, Ltd, Israel: Insightec, Ltd, Israel: Jallal Gnaim, Ph. D, CTO-Founder Yoav Medan, D. Sc. , Chief System Architect Fabian Arditti, Ph. D, R&D Manager, Alex Volovick, M. Sc, Scientist Dana Gurevich, Ph. D student. Osnat Dogadkin, M. Scientist Doudou Xu, Ph. D student Bjoern Gerold, Ph. D Student. Nizar Mishael, CPO, Bus. Dev. Yelena Vachutinsky, Ph. D, scientist Institute for Medical Science and Technology (IMSAT), and University of Dundee, UK: Prof. Andreas Melzer, MD, Director of IMSa. T Prof. Sandy Cochran, Ph. D, Deputy Director Lijun Wang, Ph. D, Head of Biol. Lab Paul Prentice, Ph. D, Scientist Ritu Maliki, Ph. D, Post-Doc The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

Acknowledgement • This research, Nanoporation, is an FP 7 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 Capsu. Tech: Dr. Jallal Gnaim, Dr. Fabian Arditti The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk

The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 7/2007 -2013) under Grant Agreement no 230674 SMIT 14. Sep. 2011 Doudou Xu d. z. xu@dundee. ac. uk