EpitopeMap RNP Mid-term Review 14 th October 2010 Dr. Iseult Lynch University College Dublin

CHEMICALS PARTITION NANOPARTICLES TAKEN UP Outside cell Inside cell Chemicals partition….. Nanoparticles processed! Significant progress in understanding role of protein corona during EpitopeMap

Mapping the Corona and Engaged Complexes along the pathway LAMP1, 48KDa 24h uptake EEA1, 180 KDa LAMP1, 48KDa EEA1, 180 KDa 20 min uptake Filippo Bertoli Magnetic core Silica shell

AMOUNT OF SILICA TAKEN INTO CELL AFFECTED MUCH MORE BY WHATS ON SURFACE THAN SIZE Protein absent Presence of protein Protein corona layer affects NPs cellular uptake

plasma% Hydrophobic surface Hydrophilic surface SiO 2 OH The intensity of most bands increase with plasma concentration Different corona at different plasma concentration PS OSO 3 - Na + OH Corona selectivity on NPs surface

Summary of Exchange Activities Total number of trips:27 No. of Host countries:5 No. of Origin countries:8 Total number of people travelled:19 Males11 Females8 PhDs7 Postdocs8 Professors4 To date, all exchanges & visits have involved 1 Steering Committee partner SC – involved in exchange visits Non-SC – involved in exchange visits SC – involved in hosting events SC – need to engage in Phase II

Summary of Events YEAR 2010 Workshop on “Microbe Protein Coronas” Helsinki, 25 – 26 March 2010; Convenor: Markus Linder (Helsinki) Conference "Nanotheranostics: Fabrication and Safety Concerns" Cyprus, April 2010; Convenor: Theodora Krasia (Nicosia) YEAR 2009 Nano-Infrastructure User Consultation Meeting Brussels, 13 November 2009; Convenor: Iseult Lynch (Dublin) Conference "Bionano: Inspiring Responsible Development for Society and the Environment" Dublin, October 2009; Convenor: Iseult Lynch (Dublin) YEAR 2007 ESF-EMBO Symposium "Probing Interactions between Nanoparticles / Biomaterials and Biological Systems: Alternative Approaches to Bio- and Nano-toxicity" San Feliu de Guixols, November 2007

QNano Research Infrastructure INDUSTRY NEUTRAL EVIDENCE BASED PROCESSES (EG ROUND ROBINS) MATERIALS QUALITY ASSURED, AND PARAMETERS REPORTED REPRODUCIBILITY DRIVEN AS A NECESSITY Helping drive new ‘safety by design’ products? REGULATOR ‘STANDARDS’ A NEW AXIS OF TRUST?

EpitopeMap Future plans Support implementation of QNano RI – Workshops & conferences on topics related to role of NP-protein corona in quantitative nanosafety assessment – Support development of best practice for nanosafety assessment / nanoregulation Facilitate beyond SoA research in NP corona – Engage new groupings – expand SC ? – Drive uptake of key advances into policy & regulation (e.g. in vitro – in vivo corona differences)

Some key publications Lynch, I., Dawson K.A. Protein-nanoparticle interactions, NanoToday, 2008, 3, (citations: 48) Lundqvist, M., Stigler, J., Cedervall, T., Elia, G., Lynch I., Dawson K. Nanoparticle Size and Surface Properties determine the Protein Corona with possible implications for Biological Impacts. PNAS, 2008, 105, (citations: 71) Dell'Orco, D., Lundqvist, M., Oslakovic, C., Cedervall, T., Linse, S. Modeling the time evolution of the nanoparticle-protein corona in a body fluid. PLoS One. 2010, 5, e Sandin, P., Schüller, V., Lynch, I., Rädler, J.O., Dawson, K.A. Time-resolved tracking of nanoparticle uptake in living cells: continuous versus pulsed exposure. Manuscript in preparation. Quinlan-Pluck, F., McManus, J,J., Cabaleiro-Lago, C., Lynch, I., Rädler, J.O., Dawson, K.A. Fluorescence Correlation Spectroscopy as a tool to track nanoparticle protein fibrillation in situ in real time. Manuscript in preparation. Hajdú, A., Baldelli-Bombelli, F., Monopoli, M., Lynch, I., Tombacz, E., Dawson, K.A. Effect of surface coating on the protein corona of superparamagnetic iron oxide nanoparticles (SPIONs). Manuscript in preparation.

Request for extension Initially programme planned from May 2007 – April 2012 (5 years) QNano RI due to start late 2010 and run for 4 years Extending EpitopeMap RNP to April 2013 would enable EpitopeMap to play a more significant role in the implementation and driving of the QNano RI, including supporting Transnational Access and Research Networking Activities. We would also like to seek additional SC members (interested expressed by UK, Portugal, Spain, France etc.)

Thank you for your attention Queries / Questions?