MRI GUIDED FOCUSED ULTRASOUND ACTIVATED NANO ENCAPSULATED TARGETED

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MRI GUIDED FOCUSED ULTRASOUND ACTIVATED NANO ENCAPSULATED TARGETED DRUG DELIVERY Doudou Xu Ph. D 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. [email protected] ac. uk

Outline • Introduction: Nanoporation Project • Thermal Sensitive Sugar Based Carrier • Nano-Sonication • 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. [email protected] ac. uk

Nanoporation is an interdisciplinary project • Pre-clinical oncology research • Cell biology • Magnetic 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. [email protected] ac. uk

MRg. FUS- Magnetic Resonance guided Focused Ultrasound Surgery • MRg. FUS combines High Intensity 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. [email protected] ac. uk

The Nano-vehicles • Sugar based nanocarrier which can increase the solubility of hydrophobic drugs 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. [email protected] ac. uk

Thermo-Sensitive Carrier (I) • Encapsulation percentage around 95%; • 40 -fold more uptake at 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. [email protected] ac. uk

Thermo-Sensitive Carrier (II) • Hyperthermia increased penetration of Doxorubicin • Hyperthermia decreased binding constant 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. [email protected] ac. uk

In vitro Sonication Machine (I) The NANOPORATION project has received funding from the European 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. [email protected] ac. uk

In vitro Sonication Machine (II) The NANOPORATION project has received funding from the European 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. [email protected] ac. uk

Nano-Sonication Doxorubicin Uptake Test Fluorescence Digraph 592. 05 nm With US (23. 42) No 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. [email protected] ac. uk

Conclusion • Optimised carrier for Doxorubicin encapsulation efficiency is over 95% • Capsu. Tech 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. [email protected] ac. uk

Future Studies • In vitro Viability test of Nano-Sonication by encapsulated Doxorubicin • In 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. [email protected] ac. uk

Our Team: Capsutech, Ltd, Israel: Insightec, Ltd, Israel: Jallal Gnaim, Ph. D, CTO-Founder Yoav 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. [email protected] ac. uk

Acknowledgement • This research, Nanoporation, is an FP 7 funded Marie Curie Industry-Academia Partnerships 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. [email protected] ac. uk

The NANOPORATION project has received funding from the European Community’s Seventh Framework Programme (FP 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. [email protected] ac. uk




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