EpitopeMap RNPMid-term Review

14th October 2010Dr. 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

Magneticcore Silica

shell

AMOUNT OF SILICA TAKEN INTO CELL AFFECTED MUCH MORE BY WHATS ON SURFACE THAN SIZE

Protein absent

Presence of protein

0 2 4 60

300

600

900

1200

Time (hours)

50nm SF 100nm SF 50nm CMEM 100nm CMEM

0 2 4 60

300

600

900

1200

Fold

incr

ease

in fl

uore

scence

0 2 4 60

300

600

900

1200

0 2 4 60

300

600

900

1200

Protein corona layer affects NPs cellular uptake

plasma%Hydrophobic surface Hydrophilic surface

SiO2

OH

OH

The intensity of most bands increase with plasma concentration

Different corona at different plasma concentration

PSOSO3

-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

Males 11

Females 8

PhDs 7

Postdocs 8

Professors 4

To date, all exchanges & visits have involved1 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 EventsYEAR 2010Workshop on “Microbe Protein Coronas”• Helsinki, 25 – 26 March 2010; Convenor: Markus Linder (Helsinki)

Conference "Nanotheranostics: Fabrication and Safety Concerns"• Cyprus, 27 - 30 April 2010; Convenor: Theodora Krasia (Nicosia)

YEAR 2009Nano-Infrastructure User Consultation Meeting• Brussels, 13 November 2009; Convenor: Iseult Lynch (Dublin)

Conference "Bionano: Inspiring Responsible Development for Society and the Environment"• Dublin, 15 - 16 October 2009; Convenor: Iseult Lynch (Dublin)

YEAR 2007ESF-EMBO Symposium "Probing Interactions between Nanoparticles /• Biomaterials and Biological Systems: Alternative Approaches to Bio- and Nano-toxicity"• San Feliu de Guixols, 3 - 8 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, 40-47. (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, 14265-14270. (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, e10949.

• 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?