nanosafe 10, nov. 16 - 18, 2010 — minatec, grenoble, france nanoparticle toxicity and cancer...

NanoSafe 10, Nov. 16 - 18 , 2010 — Minatec, Grenoble, France

Nanoparticle Toxicity and Cancer

Thomas PrevenslikQED Radiations

Hong Kong, China

1


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


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


Propose

QED Radiation from NPs is the source of UV radiation

QED = quantum electrodynamics

4


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


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


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

rn/c

f D2

For a spherical NP of diameter D and refractive index nr the equations may be written

E = hf


QM – Einstein/Hopf

0.00001

0.0001

0.001

0.01

0.1

1 10 100 1000

Wavelength - - microns

Pla

nck

Ene

rgy

- E -

eV

1

kT

hcexp

hc

E

8

0.0258 eV

NPs

Heat capacity vanishes


NPs and Biological Cells

9

Collision

DNA Damage

H2OHydroxyl Radical

NP

Biological Cell Wall

UV•

UV NP


Collisional Power

0.1

1

10

100

1000

0 500 1000 1500 2000

NP Diameter - D - nm

Col

lisio

nal P

ower

- Q

C -

nW

a v a g2

C N/M Wm,m

k Tp P D

32Q

Collision Power

10


QED Radiation ~ Source of ROS

11

0.1

1

10

100

1000

1 10 100 1000 10000

NP Diameter - D - nm

Pla

nck

Ene

rgy

- E P

- e

V

1.E+12

1.E+15

1.E+18

1.E+21

1.E+24

1.E+27E P

dNP /dt

QE

D P

hoto

n ra

te -

dNP /

dt.

Non-IonizeIonize

Silver nr = 1.35

Collision Power E dN/dt = Qc

D < 60 nm gives > 5.2 eV to produce ROS


UV Enhancement by PM

12

d

dUV

UV

NIRD

Collision

Collisions

DNA

DNA

UV Enhancement Ratio

NanoSafe 10, Nov. 16 - 18 , 2010 — Minatec, Grenoble, France 13

PM increase ROS, but oxidative stress paradigm still valid.

Biological NPs

( D < 1 micron and nr > 1.333) → UV → DNA damage

Cancer by Epithelial NPs

Exocytosis of Granules

Molecular Markers of Cancer


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.


BM Fragmentation by MMP-3


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


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

nanosafe 10, nov. 16 - 18, 2010 — minatec, grenoble, france nanoparticle toxicity and cancer...

Documents