DNA Damage by Nanoparticles Thomas Prevenslik QED Radiation Berlin and Hong Kong Enter speaker notes here. Nazarat-Taleem, Seminars, September 26, 2016

Background 1 In 2010, I gave this talk at ASME Conference in Houston. At that time, DNA damage between cells was (and still is) thought communicated at a distance by signaling and Heat  NPs was (and still is) thought to increase temperature. Show Heat  NPs  UV  DNA damage at a distance Think about this during talk 1 Nazarat-Taleem, Seminars, September 26, 2016

Introduction NPs offer significant advancements as antibacterial agents in food processing, burn treatment, sunscreen skin lotions, and treating cancer tumors. However, NPs have a darkside Over the past decades, experiments have shown NPs produce ROS of hydroxyl radicals that cause cell death and single and double strand breaks in the DNA. ROS = Reactive Oxidative Species 2 Nazarat-Taleem, Seminars, September 26, 2016

DNA and ROS Energies Direct DNA damage requires at least photolysis at UV levels. The DNA ionization potential ~ 7.5 to 10 eV. Breaking SS and DS in dry DNA > 7 eV. Indirect ROS cause SS and DS breaks by chemical reaction ~ 5.2 eV break H-OH. So, at least 5.2 eV required to produce ROS But where does energy come from? 3 Nazarat-Taleem, Seminars, September 26, 2016

Oxidative Stress Paradigm ROS correlates with NPs having diameters d <100 nm Surface-to-volume ratio = A / V = 6 / d > 60 mn/m What is the physical mechanism that links A / V  ROS? We know UVA is absorbed weakly by most biomolecules but results in photolytic generated ROS What is the UVA source? But UVA < UVB < UVC  DNA damage w/o ROS 4 Nazarat-Taleem, Seminars, September 26, 2016

DNA Damage by UV Radiation Experiments over past 20 years show DNA damage by NPs conventional UV radiation. mimics 5 Nazarat-Taleem, Seminars, September 26, 2016

Proposal Heated NPs in body fluids produce EM radiation beyond the UV that generates the ROS UV Radiation from NPs is the source of ROS No need for ROS 6 Nazarat-Taleem, Seminars, September 26, 2016

Nazarat-Taleem, Seminars, September 26, 2016 NPs  DNA damage UV DNA damage ROS DNA damage UV Heat NP No Heat Capacity No Temperature change 7 Nazarat-Taleem, Seminars, September 26, 2016

QM and QED 8 Classically, heat is conserved by temperature change. But at the nanoscale, QM requires atom heat capacity to vanish so heat cannot be conserved by an increase in temperature. QM = quantum mechanics QED conserves heat by frequency up-conversion to the NP resonance followed by the emission of non-thermal UV radiation QED = quantum electrodynamics 8 Nazarat-Taleem, Seminars, September 26, 2016

Nazarat-Taleem, Seminars, September 26, 2016 Model At the nanoscale, QED converts heat Q into UV radiation because QM precludes conservation by an increase in temperature. QED is a simple form of the complex light and matter interaction advanced by Feynman and others Heat  NP w/o heat capacity  UV radiation f = (c/n)/  / 2 = d E = h f UV Radiation /2 = d Heat Q No Temperature Change High S/V Ratio /2 9 Nazarat-Taleem, Seminars, September 26, 2016

Heat Capacity of the Atom Nazarat-Taleem, Seminars, September 26, 2016 kT 0.0258 eV Classical Physics (MD, Comsol) Nanoscale Macroscale Classical Physics (MD, Comsol) QM (kT = 0) 1900  Planck derived the QM law 1912  Debye’s phonons  h = kT  valid for  > 100 m But, phonons used in NPs ! 1950  Teller & Metropolis MD  PBC  valid for  > 100 m Today, MD used in discrete NPs ! NPs have high S/V ratios  Heat is absorbed in NP surface  EM confinement of NP atoms over nanoscale wavelengths How do NPs provide high EM confinement? No “helmut” around NP !!! 10 Nazarat-Taleem, Seminars, September 26, 2016

DNA Damage by Signaling University of Bristol claimed signaling as the mechanism by which damaged cells damage other cells at a distance Nature Nanotechnology, 5 November 2009 CoCr NPs cause DNA damage across an intact cellular barrier (CoCr from metal implants) Bare Co ions found in damaged cells as CoCr corrodes ? However, NPs  UV that passes barrier also produces Co ions 11 Nazarat-Taleem, Seminars, September 26, 2016

Nazarat-Taleem, Seminars, September 26, 2016 Bristol Experiment CoCr Particles 30 nm BeWo Cell Barrier UV Micro-porous Membrane 0.4 micron Co UV 1 mm Human Fibroblast Cells 12 Nazarat-Taleem, Seminars, September 26, 2016

Bristol Experiments 13 Co Cr NPs corrode to form Co ions Pro: Drugs that suppress signaling reduce DNA damage Co Cr NPs corrode to form Co ions Con: UV ionization of CoCr  Co ions damage DNA UV + CoCr Co + Cr UV does not penetrate microporous membrane UV absorptive drugs that block UV are consistent with drugs that suppress signaling 13 Nazarat-Taleem, Seminars, September 26, 2016

PNNL Bystander Testing Cells were stained with pink and blue dye. Only pink cells hit by alpha particles. But blue cells are also damaged? Traditional Biological Explanation: Pink cells signal blue cells of damage Evidence for Signaling ? Or Pink chromosomes produce UV that damages blue chromosomes? UV PNNL – Bystander Program 14 Nazarat-Taleem, Seminars, September 26, 2016

PNNL Experiment Macroscopic Pink Cells hit by  particles increase in temperature Nanoscopic Pink chromosomes do not increase in temperature, but emit UV that is absorbed by Blue chromosomes at a distance Both Pink and Blue chromosomes fragment under high hydrostatic stress from absorbed UV Bystander effect is caused by UV produced in chromosome NPs 15 Nazarat-Taleem, Seminars, September 26, 2016

Conclusions 16 Unknown energy source > 5 eV is required to form ROS Only UV from NPs has energy to form ROS No need for ROS, only UV Need experimental verification that heat  UV Bristol and PNNL experiments show UV from NPs is the unknown energy source 16 Nazarat-Taleem, Seminars, September 26, 2016

Nazarat-Taleem, Seminars, September 26, 2016 Questions & Papers Email: nanoqed@gmail.com http://www.nanoqed.org Enter speaker notes here. 17 Nazarat-Taleem, Seminars, September 26, 2016