NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France Nanoparticle Toxicity and Cancer Thomas Prevenslik QED Radiations Hong Kong, China 1

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France Introduction NPs offer significant technological advancements as antibacterial agents in food processing, reducing infections in burn treatment, sunscreen skin lotions, treating cancer tumors, etc. However, NPs have a darkside 2 Over the past decade, experiments have shown natural or man- made NPs produce ROS of hydroxyl radicals that cause apoptosis/cell death and SS and DS breaks in the DNA. ROS = Reactive Oxidative Species

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France Oxidative Stress Paradigm ROS are correlated with the surface area of NPs <100 nm Problem – Coarse PM > 300 nm enhance ROS Surface activity of NPs causes ROS Problem – ROS require > 5.2 eV to form OH radicals not possible with Surface activity OH radicals need UV, but what is the UV source? 3

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France Propose QED Radiation from NPs is the source of UV radiation QED = quantum electrodynamics 4

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France How do NPs lead to Cancer? Cancer does not occur without DNA damage Experiments over past decade show DNA damage by NPs mimics that by conventional UV Thus, NPs produce UV NPs most likely cause Cancer 5

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France QED Radiation Classically, heat (EM energy) is conserved by an increase in temperature. But at the nanoscale, QM restricts the atom to vanishing heat capacity so heat cannot be conserved by an increase in temperature. QM = quantum mechanics QED allows absorbed heat to be conserved at the nanoscale by frequency up-conversion to the TIR resonance of the NP followed by the emission of non-thermal UV radiation 6

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France QM and QED Photons 7 QM restricts the heat content of atoms depending on temperature and TIR confinement given by the Einstein- Hopf relation for harmonic oscillator For a spherical NP of diameter D and refractive index n r the equations may be written E = hf

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France QM – Einstein/Hopf eV NPs Heat capacity vanishes

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France NPs and Biological Cells 9 UV NP

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France Collisional Power Collision Power 10

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France QED Radiation ~ Source of ROS 11 Collision Power E dN/dt = Q c D 5.2 eV to produce ROS

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France UV Enhancement by PM 12

UV Enhancement Ratio NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France 13 PM increase ROS, but oxidative stress paradigm still valid.

Biological NPs ( D 1.333) → UV → DNA damage Cancer by Epithelial NPs Exocytosis of Granules Molecular Markers of Cancer NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France 14

Cancer by Epithelial NPs Epithelial tissue protects the breast, prostate, colon, and lung Organized by a submicron thick < 100 nm basement membrane (BM) that upon fragmenting is associated with the spread of tumors Flat submicron thick NPs ~ Similar to Graphene flakes MMP-3 enzymes induce the BM fragmentation to produce UV as the fragments move in the body. NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France 15 7

BM Fragmentation by MMP-3 NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France 16 The MMP-3 enzyme causes normal cells to produce the Rac1b protein that is found only in cancers The Rac1b is a small protein that once formed produces UV causing the Cancer growth by damaging nearby DNA

NanoSafe 10, Nov , 2010 — Minatec, Grenoble, France Conclusions NP Toxicity is caused UV radiation Oxidative stress paradigm is valid Toxicity enhanced by nearby PM All NPs ~ Natural, Man-made, Biological ~ are Toxic Questions Is UV induced NP toxicity preventable? Are Cancer drugs that suppress UV possible? 17