1. Nanotoxicity and Nanosafety; the nanomedicine perspective Recommendations from the Nanomedicine Community 1 Adriele Prine-Mello Trinity College Dublin, Ireland Chair of Characterization and Toxicology Working Group

2. Kicking off on the perspective ETPN Submitted nanoparticle selection Physical characterization Chemical characterization In vitro assays In vivo assays Clinical use Pre-clinical approval of nanoparticles Intentional administration NanoSafetyCluster Particle synthesis Particle characterization in-situ and ex-situ Mechanism of interaction Particle exposure assessment (in vitro, in vivo, in silico) Nanosafety Impact of exposure to nanoparticles Non intentional exposure 7 th nanoTOX2014 Antalya 23-26 April 2014

3. 3 Everything is Relative One of the most toxic drugs known Rat i.v. DL50 = 8 mg/kg Insecticide to treat pet Dog i.v. DL50 = 7 mg/kg Ketoconazale, fungicide to treat dandruff Man oral DL50 = 45 mg/kg Introduction Toxic drugs known Rat i.v. DL50 = 85 mg/kg 7 th nanoTOX2014 Antalya 23-26 April 2014

4. Improving the Risk-Benefit Ratio… Risk Benefit …of currently-available medical treatment with nanotech is possible! Nano ©TCD 2014 Nanomedicine perspectives TCD © 2014 – Prina-Mello / Movia

5. Nanomedicine tiered approach Tier 2 Tier 3 » Physico-chemical characterisation » Internalization: mechanism and time-dependence » Cytotoxicity » Biodegradation » Biocompatibility » Targeted drug delivery Shell-coated NPs Purpose-specific functionalized NPs Safe-by-design Risk Benefit Adapted from Movia D. et al., Biomaterials, 2014, 35, 9, 2543-2557 ©TCD 2014 WG T&CWG T&C WG T&CWG T&C

6. Big deals in nanomed in 2013 : > 1 Billion US$ 6 180M US$ 210M US$ 200M US$ 7 th nanoTOX2014 Antalya 23-26 April 2014

7. The European approach to improve translation …..including toxicity and safety 7 th nanoTOX2014 Antalya 23-26 April 2014

8. ETPN Translational process and focus (WG T&C) Translation process Design Synthesis Clinical tests Clinical tests Nano characterisation Nano characterisation cGMP manufacturing Accelerating translation of engineered nano-products for medicine applications to medicinal products Proof of concept Toxicity Safety PK PD Risk/Benefit analysis Validation to Standards QC, QA Certification Nanomedicine Commons Extras 7 th nanoTOX2014 Antalya 23-26 April 2014

9. Translation process Full characterisation Clinical trials Scale up Manufacturing Approval Proof of concept NSC: Database Database Expertise Expertise Models Models Experience Experience Large EU network Large EU network NSC: Regulatory Regulatory EHS EHS 7 th nanoTOX2014 Antalya 23-26 April 2014

10. ETPN Translation hub 7 th nanoTOX2014 Antalya 23-26 April 2014

11. Impacts on EU Economic –>500 SMEs in nanomedicine in Europe –Nearly 250 “nano”-products are used or tested in humans Societal –Diagnostics tools and better healtcare treatments for a more targeted and more personalised medicine with less side-effects for a more cost-effective healthcare ETPN Impact on H2020 White paper SRIA

12. For more information, contact: secretariat@etp-nanomedicine.eu Consult www.etp-nanomedicine.eu to Download reports and documentsDownload reports and documents Find further informationFind further information Become a memberBecome a member …

13. For more information: Adriele Prina-Mello, Msc, PhD Andreas Falk, MSc E: prinamea@gmail.com E: Andreas.Falk@bionanonet.atAndreas.Falk@bionanonet.at P. +353 1 896 3259W: www.bionanonet.atwww.bionanonet.at Linkedin: adriele-prina-mello/1/393/b13 Google scholars: Adriele Prina-Mello Research Gate profile: Adriele_Prina-Mello Thank you for your attention