Sustainable and smart nanomaterials will enable nanotechnologies

1. Sustainable and smart nanomaterials will enable nanotechnologies Paul J.A. Borm

2. Chemelot campus, 800 ha, 80 companies Incl DSM, SABIC

3. CEO Products Production Profit Nanoparticles As tools Prof People Planet Papers Nanoparticles as Objects of study J. Miro, self-portrait

4. Intentionally produced NP • already on the market • Newly engineered • Unintentionally produced NP • Combustion • Nucleation No added value, extra cost Considerable health risks New products, applications High added value Nanomedicine: Intended exposure High dose, low risk

7. Risk = hazard x exposure Hazard: the “ability” of a chemical to cause harm Risk: the “probability” it will do so

8. Company policies for handling nanomaterials Defined by 9 out of 32 companies (24%) Others on project level 3 most important elements: Pre-emptive choice on specific nanoparticles Handling all nanomaterials as toxic substances (safety principle) Choices on the physical form of nanoparticles Borm, Houba & Linker (2008) Survey on best practices in handling nanomaterials in Dutch industry.

9. Occupational hygiene strategies by approach

10. Risk = hazard x exposure Hazard: the “ability” of a chemical to cause harm Risk: the “probability” it will do so

11. Sources of evidence: a Bermuda Triangle Combustion NP Epidemiology Toxicology ? Bulk industrial NP Engineered NP Nanomedicine ?

12. In words: Most of the evidence for human effects of NP is generated using unintentionally produced combustion Nanoparticles. Effects of manufactured Nanoparticles have mainly been studied with a small set of particles already on the market for decades (carbon black, TiO2, FeO) and more recently on carbon nanotubes.

13. General paradigms in nanoparticle toxicity based on inhalation Size matters for many dynamic and kinetic issues. Inflammation is the key hallmark in effects. Surface area is the best metric for inflammation. For other effects no such consensus is present. At fine size, aggregates of nanoparticles have a larger effect than one fine particle of the same material. Aggregates of nanoparticles cannot be dissociated in epithelial lining fluid. Does that impede single NP uptake? Size is the main driver for current studies. Little data is available that allow bridging to other routes of exposure or materials

14. Platelet aggregation by NP PM and carbon nanoparticles Have similar hazards

16. Customized nanotools and Assemblies, based on Magnetic properties Drug Matrix Linker Imaging tool Homing device Assembly

17. Drug delivery platforms on magnetic capture Applied successfully In animal studies. Krukemeyer et al (2008) In preparation

18. Mitoxantrone-loaded Iron nanoparticles. Size: 120 nm Surface: dextrane Zeta-potential: -34 mV Load MT: 20 ug/mg Dose: 1 mg/kg BW Photo’s courtesy dr. Krukemeyer

19. Patient KL, treated with mitoxantrone-FF(100 mg/m2) liver metastasis reduced from 14.9 to 8.0 cm3 30.05.2008 04.07.2008

20. No hair loss • No gastro-intestinal complications • Normal kidney function • Temporal loss of leucocytes and thrombocytes. • iron accumulation in the spleem

21. Intravenous delivery of engineered NP Needs to study a series of questions: • what happens to the FeO particles upon release from coatings? • Is the surface active to bind endogenous proteins? • Are NP being degraded/excreted or reach other targets. • Do circulating FeO particles affect platelet aggregation, thrombosis or any other vascular condition?

23. MagnaFy: making devices visible • Immobilize NP in polymers and composites • Use magnetic properties and signal distortion: markers are magnified and easily visible • No release of contrast agent in body • Small volume and therefore no heating • Application to existing medical devices

24. Medical imaging-guidewires Application in renal stenting

25. MagnaFy: Biocompatibility and safety Coated rods were found to be biocompatible in blood samples. No wearing of markers in guide-wires after application in vivo In worst-case damage of marker would cause release of iron-oxide nanoparticles. The iron oxide nanoparticles in our coating our non-toxic and biocompatible to relevant target systems. Iron oxides are used as SPIONS and injected on purpose as contrast agent. Matrix, iron-oxide and hydrophilic coating are fully biocompatible. Residence time of devices is usually low ( < 15 min) and are removed from the body No release from device as applied in active imaging

26. Nanomedicine as a benchmark? • Data on toxicity of (drop-out) engineered nanoparticles from • nanomedicine and its resulting conceptual understanding • can be used as a benchmark for all nanomaterials: • Learn from properties of drop-outs • Learn from placebo groups • Effects at high (intentional) doses • Acute effects and chronic pathology • Use of sensitive and well-characterized models • Generate conceptual understanding • Bridge know-how to other materials and sectors

27. NanoMedicine mar help to fullfil Nanotechnology essential needs: • Guide to safe and sustainable (nano)materials • Set standards for handling and best-practices • Generate amended regulation and tests, through it sensitive models • May create success stories that show the benefit-risk balance in a proper way.

28. NanoScreen: our solution to your question • Content: • Screen your product for nanoparticles and exposure potential • Screen and monitor your workers for particle exposure and uptake • Screen the biocompatibility of your products and components. • Screen your best-practices A business to business service from one user to another. You learn from our experience