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

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. Heat Capacity of the Atom Nazarat-Taleem, Seminars, September 26, 2016
kT 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

12. 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

13. 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

14. 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

15. 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

16. 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

17. 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

18. Nazarat-Taleem, Seminars, September 26, 2016
Questions & Papers
Enter speaker notes here. 17
Nazarat-Taleem, Seminars, September 26, 2016