Download What is nanotechnology?

Nanotoxicology
Wesley E. Smith, Ph.D.
Senior Fellow
Center for Ecogenetics and Environmental Health
University of Washington
[email protected]
http://thereadingroom.epsilonfoundation.com.au/technology/nano-tech-godzilla/
Outline
What is nanotechnology?
What is nano?
Where is nano?
What is the state of nanotoxicology?
In vitro methods
In vivo approaches
What is happening at the UW?
What is nanotechnology?
How big is a nanometer?
Quantum dot ~10-20nm
Adapted from:http://www.nano.gov/html/facts/The_scale_of_things.html
How big is a nanometer?
Quantum dot ~10-20nm
Adapted from:http://www.nano.gov/html/facts/The_scale_of_things.html
What is nanotechnology?
“Nanotechnology is the understanding and control of
matter at dimensions between approximately 1 and
100 nanometers, where unique phenomena enable
novel applications”
Involves multiple disciplines, including science,
engineering and technology
“Wet”-involving aqueous systems
“Dry”-surface chemistry, semiconductors
Computational-modeling nanosystems
Nanosized particles (NSPs)
Categories of Nanotechnology
(Engineering classifications)
Oxides: TiO2, ZnO, CeO2, Fe3O4, SiO2
Metals: Ag, Co, Ni, Fe, Au, Cu
Carbon-based: Nanotubes (single-, double- and
multiwalled), Fullerenes (C60), Nanofibers
Quantum Dots: Fluorescent semiconductor NM
Macromolecules: Branched polymeric organic molecules
Self-assembled: Lipids, metal oxides, organic molecules
self assemble based on inherent physical properties
(ICON, 2008)
Current consumer applications of nanotech
Nano-Care® Stress free Khakis-(Gap)
“Nanoémulsion Peaux Sensibles
Calming Emulsion”-(Chanel)
“The Samsung 65-nm 8-Gbit NAND
flash (K9G8G08U0M)”-(Apple)
 Public inventory:
http://www.nanotechproject.org/inventories/consumer/
Where is nanotechnology?
http://www.nanotechproject.org/maps/mappage.html
What is the state of
Nanotoxicology?
Federal oversight
The National Nanotechnology Initiative (NNI) has
provisions for funding for environmental, health, and
safety studies (EHS)
Under the Nanoscale Science, Engineering, and
Technology subcommittee (NSET), Nanotechnology
Environmental Health Implications working group
(NEHI WG) functions as an interagency forum on
understanding potential risks of nanotech.
NNI EHS Document
Strategy for Nanotechnology-related Environmental, Health,
and Safety Research
In FY2006, $68 million invested into 246 projects at 7
agencies.
Summarizes primary research categories:
– Instrumentation, Metrology, and Analytical Methods
– Nanomaterials and Human Health
– Nanomaterials and the Environment
– Human and Environmental Exposure Assessment
– Risk Management Methods
Strategy for Nanotechnology-related
Environmental, Health, and Safety research
Who is responsible?
1
National Institute for Standards and Technology (NIST)
 Instrumentation, metrology, and analytical methods
2
National Institutes of Health (NIH)
 Nanomaterials and human health
3
Environmental Protection Agency (EPA)
 Nanomaterials and the environment
4
National Institutes of Occupational Safety and Health (NIOSH)
 Human and environmental exposure assessment
5
Food and Drug Administration (FDA)
 Risk management (also EPA)
Do nanomaterials present a risk to
human and environmental health?
The very same physical and chemical characteristics of
nanomaterials that give promise, also have the potential for
peril.
Effects are not well characterized.
Ultrafine particles (UFPs) generally cause more toxicity in
lung models
Reactivity of some particles increases as surface area-volume
ratio increases
Represents a very important need for research.
Who is at risk?
Humans
Workers
Consumers
Susceptible: elderly and children
Wildlife
Aquatic life
Terrrestial life
Ecosystem
Flora
Fauna
Problems to overcome
“Dose makes the poison”-what do we measure?
No consensus on measuring nanoparticles (metrologysurface area, volume)
functionalization moieties -SA is probably most relevant
Heavy metals (Cd2+, Hg2+, etc)-mass
Characterizing aggregation and/or agglomeration
Definitions of dispersion of nanoparticles
Primary particle: smallest identifiable subdivision in a
particulate system, may be subunits of aggregates
Aggregate: a cohesive mass consisting of particulate subunits
Hard Aggregate: an aggregate that cannot be easily dispersed (in
a liquid) by the application of moderate mechanical agitation
(shaking, stirring, or ultrasonication) and/or mild chemical
treatment, consist of subunits which have been chemically
bonded or fused
Agglomerate: in a suspension, an aggregate held together by
physical or electrostatic forces
NIST Guide (Use of Nomeclature in Dispersion Science and Technology, V. A. Hackley and C.F. Ferraris, National
Institutes of Standards and Technology, Special Publication 960-3, August 2001, 72, pp. 5)
Qdot size distribution: Williams E Media
WEM
(filtered, no
Qdots)
WEM
(filtered, 10
nM Qdots)
WEM
(unfiltered,
10 nM Qdots)
Human toxicology
In vitro models
MTT, LDH
Glutathione measurements
Oxidative stress
In vivo models
Histopathology
Clinical chemistry
“-omic” (i.e. Proteomics, genomics, metabolomics,
physiomics, etc.) analysis of samples from both in vitro
and in vivo models.
In vitro methods for assessing risk,
exposure, and toxicity
Cell-based assays with nanomaterials
Adhesion/uptake
Trafficking
Cell response
Toxicity/viability
Phenotype influence/stress
Macromolecule interactions with nanomaterials
Adsorption
Aggregation
Opsonization
Kinetic and chemical effects
In vivo models:
toxicokinetics
Many barriers
Extracellular: organ-level
Epithelial barrier:
Circulation, blood components
Reticuloendothelial system (RES)
Intracellular
Cell membrane
Endosomal and nuclear membrane
DNA gene release and integration
In vivo models:
toxicodynamics
Site of toxicity
Organ
Tissue
Cell
Intracellular
Cell membrane
Endosomal and nuclear membrane
DNA gene release and integration
Environmental Toxicology
Research at the UW
Toxicology of Quantum
Dots
Kavanagh (DEOHS)
Gao (BIOE)
Multiple in vitro cell lines
Transgenic mice
Various routes of
exposure
Applications of Qdots
Medical imaging
Cancer
Diagnostics
Therapeutics
Biological imaging agent
“Tag” proteins
Monitor cellular uptake
Gao, Nature (2004)
Why are Qdots special?
Why examine the liver?
 Primary site of xenobiotic
metabolism
 Common site of toxicity
 Resident macrophages sequester
bacteria from gut
http://www.flickr.com/photos/mitopencourseware/
Architecture of liver sinusoid
http://www.flickr.com/photos/mitopencourseware/
Experimental setup
Dose-response relationships evaluated:
1.
2.
3.
4.
Uptake
Viability (MTT)
GSH levels
Cell death
Disposition of Qdots in cultured human
hepatocytes
Summary and conclusions
Qdots are sequestered by a subpopulation of cells in primary
human hepatocyte cultures
Stable Qdots have no effect on viability of human
hepatocytes in vitro
Qdots result in slightly increased cell death in HepG2
carcinoma cells
Thus far, this preparation of Qdots does not appear to be
overtly hepatotoxic. However, there is evidence that suggests
the possibility of perturbating normal physiological function
in scavenger cells (macrophages, Kupffer, etc)
Future directions
Coordinated effort to standardize methods
Metrology
In vitro assays
In vivo assays
Communication between (and among) disciplines is necessary
More data is needed
Funding ($$$) is necessary to make this happen