OVALS Talk 432009

1
OVALS Conference April 3, 2009 Dayton, Ohio
Nanoparticles, Toxicity, Characterization and
Sensors
James F. Leary, Ph.D. SVM Endowed Professor of
Nanomedicine Professor of Basic Medical Sciences
and Biomedical Engineering Member Purdue Cancer
Center Oncological Sciences Center Bindley
Biosciences Center Birck Nanotechnology
Center Email jfleary_at_purdue.edu
2
Purdue Universitys new 350 M multidisciplinary
Discovery Park dedicated Fall, 2005
Weldon School of Biomedical Engineering (2006)
New structural biology center (now under
construction) (2009)
3
http//www.nanohub.org/nanomedicine
4
http//nanohub.org/resources/2691
Nanotechnologies, Science and Society Promises
and Challenges
James F. Leary, Ph.D. SVM Professor of
Nanomedicine, Professor of Basic Medical
Sciences and Biomedical Engineering Department
of Basic Medical Sciences, School of Veterinary
Sciences Weldon School of Biomedical Engineering,
Birck Nanotechnology Center, Bindley Biosciences
Center, Oncological Sciences Center Purdue Cancer
Center Purdue University West Lafayette,
Indiana Email jfleary_at_purdue.edu
5
Nanotechnologies and Healthcare
We have come a long way
Art Da Vincis Vitruvian Man 1490
but we still have so far to go!
6
Some ways that nanotechnologies will impact on
healthcare

• Greatly improved directed therapies for
  treating cancer using new nano- drug/gene
  delivery systems
• Tiny implantable devices to monitor health.
• New point-of-care and home healthcare devices.
• Tiny implantable devices with nanobiosensors to
  treat chronic diseases (diabetes, cardiovascular,
  arthritis, Parkinsons disease, Alzheimers
  disease,) with fewer side-effects.

7
Why does Nanomedicine Represent a Huge Promise
for Health Care?Earlier diagnosis increases
chances of survival. By the time some symptoms
are evident to either the doctor or the patient,
it may be already too late.

• Conventional medicine is reactive to tissue-level
  problems that are happening at the symptomatic
  level. Nanomedicine will proactively diagnose and
  treat problems at the molecular level inside
  single-cells, prior to traditional symptoms, and
  hopefully prior to irreversible tissue and organ
  damage.
• Conventional medicine is not readily available to
  much of humanity because it is labor-intensive
  and that labor is sophisticated and expensive.
  Nanomedicine will be much more preventive,
  comparatively inexpensive because it will
  minimize use of expensive human experts, and can
  be more readily mass produced and distributed.

8
Preventing cancer at the single cell level using
nanosystems?
The current boundary between very early detection
and prevention will blur. Curing cancer may not
be possible, but treating it as a chronic disease
may well be possible.
9
A Personal, futuristic (5-15 years from now)
perspective of the impact of nanotechnologies on
healthcare
Engineering Nanomedical Systems for Directed
Therapies
10
The Progression of Medicine
Conventional Modern Medicine
Personalized or Molecular Medicine
Nanomedicine Single-cell Medicine
11
Features of Nanomedicine

• Beyond the obvious application of nanotechnology
  to medicine, the approach is fundamentally
  different
• Nanomedicine is a nano- approach NOT just due
  to the nano size. It is the nanotechnology
  bottoms-up rather than tops-down approach to
  medicine.
• Nanomedicine uses nano-tools (e.g. smart
  nanoparticles) that are roughly 1000 times
  smaller than a cell (knives to microsurgery to
  nanosurgery )
• Nanomedicine is the treatment or repair
  (regenerative medicine, not just killing of
  diseased cells) of tissues and organs, WITHIN
  individually targeted cells, cell-by-cell.
• Nanomedicine can combine use of molecular
  biosensors to provide for feedback control of
  treatment and repair. Drug use is targeted and
  adjusted appropriately for individual cell
  treatment at the proper dose for each cell
  (single-cell medicine).

12
Interactions Between Technologies for Development
of Nanomedical Systems

• Nanoparticle fabrication and quality control labs
• Nanochemistry
• Dynamic Light scattering sizing
• Zeta Potential
• Atomic Force Microscopy

• Cell and intracellular targeting labs
• Flow cytometry
• Imaging (laser opto-injection and
• ablation) cytometry
• Confocal (one- and multi-photon analysis)

• Transient Gene Therapy (gene drugs)
• Construction of therapeutic genes for
• specific biomedical applications
• Animal testing/comparative medicine
• Human clinical trials

• Biosensor Labs
• Biosensor molecular biology
• Results evaluated in targeting labs

• Nanomaterials biocompatibility labs
• Microscopy/image analysis/LEAP
• Gene expression microarray analyses

13
MOLECULAR CYTOMETRY FACILITY - 2009
BIONANOTECHNOLOGY
BIO-INSTRUMENTATION

• Engineering Nanomedical
• Systems1,2,3,5,8,

• High-throughput cytometry1,2,6, 7,

• Microfluidic cytometer/sorter1,2,3,7,

• Nanostructure characterization
• ( XPS, AFM, TEM)2,3,5,8,

• LEAP interactive molecular imaging/sorting/opto-i
  njection1,6,9,

• Nanomaterials/chemistry2,3,5

• In-vitro/In-vivo molecular imaging (optical,
  MRI, thermal)1,2,5,8,10,

• Biomolecular sensors2,5,6,9

CYTOMICS

• Peptide, aptamer, gene synthesis,
  screening1,2,3,5,6,9,

• Magnetic sorting1,2,3,5,

• Circulating cancer cells
• (breast prostate cancer, cancer stem
  cells)1,2,5,6,8

• SPR1,2,3,4,7,

• Detection of pathogens1,2,3,4,7,

Graduate Students 4 Seale-Goldsmith 5 Zordan 6
Grafton 7 Haglund 8 Eustaquio 9 Key
Faculty Staff 1 Leary (Director) 2 Reece 3
Cooper Collaborators

• Regenerative medicine
• (gene expression silencing)1,2,6,9

• Stem/progenitor cell isolation
  characterization1,2,6,9,

• Animal studies2,5,8,

• Existing areas

• New areas

14
Biomimicry Can Nature Provide Some of the
Answers?
Viruses know how to perform a multi-step targeted
process to infect cells, use the host cell
machinery to produce gene products, and make
copies of themselves. What if we could make a
synthetic good virus that could deliver
therapeutic gene templates to specific cells, and
use the host cell machinery to produce
therapeutic genes to perform regenerative
medicine in a cell and cure disease at the single
cell level (and NOT make copies of themselves!) ?
15
Concept Smart Nanomedicine Systems with Control
of Gene/Drug Delivery within Single Cells
Cell targeting and entry
Intracellular targeting
Therapeutic genes
Magnetic or Qdot core (for MRI or optical imaging)
Biomolecular sensors (for error-checking and/or
gene switch)
Targeting molecules (e.g. an antibody, an DNA,
RNA or peptide sequence, a ligand, a
thioaptamer), in proper combinations for more
precise nanoparticle delivery
Leary and Prow, PCT (USA and Europe) Patent
pending 2005
16
The Multi-Step Targeting Process in Nanomedical
Systems
17
Example of multilayered magnetic nanoparticle for
in-vivo use
Prow, T.W., Grebe, R., Merges, C., Smith, J.N.,
McLeod, D.S., Leary, J.F., Gerard A. Lutty, G.A.
"Novel therapeutic gene regulation by genetic
biosensor tethered to magnetic nanoparticles for
the detection and treatment of retinopathy of
prematurity" Molecular Vision 12 616-625, 2006
18
One Solution to the Problem of Targeted Drug
Delivery
Nanofactories
Dont try to guess the proper amount of drug for
each cell. Manufacture it to the needs of that
specific cell. With upstream biomolecular
switches and feedback control, it doesnt matter
how many nanoparticles are able to successfully
target to a rare cell in-vivo. The total output
of therapeutic genes from all targeted
nanoparticles will self regulate to the proper
dose for that cell.
19
Concept of nanoparticle-based nanofactories
(NF) manufacturing therapeutic genes inside
living cells for single cell treatments
Multilayered nanoparticle
cell
NF
cell membrane
cytoplasm
Therapeutic gene/drug
Gene manufacturing machinery
nucleus
Molecular Biosensor control switch
NF
The nanoparticle delivery system delivers the
therapeutic gene template which uses the host
cell machinery and local materials to manufacture
therapeutic gene sequences that are expressed
under biosensor-controlled delivery.
20
Dealing with the dosing problem Concept of
nanoparticle-based nanofactories
feedback-controlled manufacturing of therapeutic
genes inside living cells for single cell
treatments using engineered nanosystems
Multilayered targeted nanosystem
cell
MNP
cell membrane
cytoplasm
Therapeutic gene/drug
Gene manufacturing machinery
Molecular Biosensor control switch
Specific molecules inside living diseased cell
being treated with manufactured genes
nucleus
Feedback control
21
Efficient Gene Transfer with DNA Tethered
Magnetic Nanoparticles
PCR product bioconjugated to magnetic nanoparticle

SPIO
Magnetic nanoparticle tethered with DNA
Lipid coated magnetic nanoparticles tethered with
DNA
Lipid


Add to cell culture
22
Tethered Gene Expression on Magnetic
Nanoparticles for Nanomedicine
1. Prow, T.W., Smith, J.N., Grebe, R., Salazar,
J.H., Wang, N., Kotov, N., Lutty, G., Leary, J.F.
"Construction, Gene Delivery, and Expression of
DNA Tethered Nanoparticles" Molecular Vision 12
606-615, 2006a. 2. Prow, T.W., Grebe, R.,
Merges, C., Smith, J.N., McLeod, D.S., Leary,
J.F., Gerard A. Lutty, G.A. "Novel therapeutic
gene regulation by genetic biosensor tethered to
magnetic nanoparticles for the detection and
treatment of retinopathy of prematurity"
Molecular Vision 12 616-625, 2006b.
23
Multilayered iron oxide superparamagnetic
nanoparticles for in-vivo use as theragnostic
agents (diagnostics using targeted MRI contrast
agents and therapeutics using apoptosis-inducing
peptides
Prow, T.W., Grebe, R., Merges, C., Smith, J.N.,
McLeod, D.S., Leary, J.F., Gerard A. Lutty, G.A.
"Novel therapeutic gene regulation by genetic
biosensor tethered to magnetic nanoparticles for
the detection and treatment of retinopathy of
prematurity" Molecular Vision 12 616-625, 2006
24
Athymic Mouse Study

• Distribution in nude mice with SKBR3 breast
  cancer xenografts
• NPs with target sequence directed to SKBR3 cells
• Inject NPs via tail vein and via peri-tumoral
  injection
• At euthanasia, harvest xenograft tissue and major
  organs detect NPs

25
Some in-vivo biodistribution studies In-vivo
peptide targeting of nanoparticles to human
breast cancer cells in nude mice
26
Theragnostics (simultaneous therapeutics and
diagnostics)
Ferric oxide nanoparticles have already been
FDA-approved for human-use MRI (Magnetic
Resonance Imaging( procedures. While most use of
nanoparticles are un-guided the new wave of
guided (peptide or antibody-guided), targeted
nanoparticles will quickly become the accepted
medical practice because it can vastly reduce the
total dose exposure, thereby lowering side
effects and toxicity. MRI allows for deep
in-vivo imaging of nanomedical systems for
diagnostics and periodic therapeutic monitoring
(e.g. can compute actual tumor shrinkage).
27
http//www.nanohub.org/resource_files/2007/10/0338
8/2007.09.14-choi-kist.pdf
28
Multilayered, Multifunctional Nanomedical Systems
A Combination Product?
29
CDER-FDA Jurisdiction of Nanomedical Systems?
30
The need for single cell measures of nanotoxicity

• There is more than one way for a cell
• to die...
• B. "Necrosis" vs. "Apoptosis"
• C. There are other forms of "toxicity"
• Some other challenges in measuring
• toxicity of nanomaterials

31
Some Challenges in Evaluating the Toxicity of
Nanomaterials

• Toxicity of nanomaterials may be different from
  its elemental forms
• Toxicity may change with exposure to light, ph
  changes, etc.
• Toxicity is frequently masked by biocoatings
  which may be stripped at different rates by
  different cell types
• Toxicity needs to encompass assays beyond
  simple, rapid cell death, including apoptosis,
  cell proliferation, cell differentiation, changes
  in cell function, etc.
• How do we evaluate multi-component nano
  platform technologies, e.g. nanodelivery systems
  so they can be re-used.

32
Necrosis vs. Apoptosis mechanisms
A. Necrosis is unplanned "cell injury" B.
Apoptosis is planned "programmed cell
death" C. Why it is important to distinguish
between necrosis and apoptosis
33
Some single cell assays for necrosis and apoptosis
A. Dye exclusion assays for necrosis B. TUNEL
assays for late apoptosis C. Annexin V assays
for early apoptosis D. COMET assays for DNA
damage and repair E. Light scatter assays
34
Nanotoxicity in vivo some additional challenges

• A. Single cell nanotoxicity, plus potential
  disruption of functioning cell networks.
• Accumulations of nanoparticles can change
  toxicity locally to tissues and organs.
  Aggregates may be even more toxic.
• Filtration issues of nanoparticles size
  matters toxicity to liver and lung

35
Safety / Toxicity

• In rat studies, monitor for toxic
  effects. Clinical signs of toxicity CBC,
  serum biochemical profiles Post mortem exams

But according to a recent study, most people are
not rats!
36
Nanotechnologies, nanotoxicity and the Environment
37
Consumer Nano-Products
38
Examples (out of hundreds) of nano consumer
products (not an endorsement of these products!)
First Response Home Pregnancy Test by
Carter-Wallace
PERSONAL
Nano Cosmetics by SongSing Nano Technology Co.,
Ltd.
Zelens Fullerene C-60 Eye Cream by Zelens
Eagle One Nanowax by Eagle One
HOUSEHOLD GOODS
Antibacterial Kitchenware by Nano Care
Technology, Ltd.
Antibacterial Pet Products by Nano Care
Technology, Ltd.
Dockers Go Khaki by Dockers
CLOTHING
Eddie Bauer Water Shorts by Eddie Bauer
AccuFlex Evolution Golf Shaft by Accuflex
SPORTS/RECREATION
Stealth CNT Baseball Bat by Easton Sports, Inc
Wilson nCode Tennis Rackets by Wilson
Atomic Snow Izor Skis by Atomic Snow
http//www.nanotechproject.org/index.php?id44
39
True Nano-products versus Masqueraders

• There are several true advantages to a nano
  approach in products
• Nanoparticles can fill in porous spaces in other
  materials and make them much stronger for only
  a very small increase in weight
• Nanoparticles tend to shed water and prevent
  staining of surfaces
• Nanoparticles can change color and other
  properties in response to temperature and other
  environmental factors
• Nanoparticles on surfaces can create no-stick
  or, at least, low-stick surfaces
• Silver nanoparticles tend to kill bacteria and
  can limit bacterial contaminations and odors

40
Assessing the environmental impact of emerging
nanotechnologies
WASHINGTON, DCLife cycle assessment (LCA) a
cradle-to-grave look at the health and
environmental impact of a material, chemical, or
productis an essential tool for ensuring the
safe, responsible, and sustainable
commercialization of nanotechnology, U.S. and
European experts conclude in a new report issued
today. With the number of nanotechnology-enabled
products entering the market expected to grow
dramaticallyfrom 30 billion in 2005 to 2.6
trillion in global manufactured goods using
nanotechnology by 2014numerous uncertainties
exist regarding possible impacts on the
environment and human health, the international
authors observe in Nanotechnology and Life Cycle
Assessment A Systems Approach to Nanotechnology
and the Environment http//www.nanotechproject.org
/111/32007-life-cycle-assessment-essential-to-nano
tech-commercial-development
41
Little is currently known about the toxicity of
nanomaterials
Figure 1-1 Possible exposure routes for
nanoparticles based on current and potential
future applications (adopted from The Royal
Society Royal Academy of Engineering 2004)
The lack of toxicity data specific to
nanomaterials is a repeating theme in this and in
other studies related to nanotech environmental,
health, and safety concerns, says Andrew
Maynard, chief scientist for the Project on
Emerging Nanotechnologies. Nanotechnology is no
longer a scientific curiosity. Its products are
in the workplace, the environment, and home. But
if people are to realize nanotechnologys
benefitsin electronics, medicine, sustainable
energy, and better materials for building,
clothing and packagingthe federal government
needs an effective risk research strategy and
sufficient funding in agencies responsible for
oversight to do the job.
http//www.nanotechproject.org/111/32007-life-cycl
e-assessment-essential-to-nanotech-commercial-deve
lopment ( NanoLCA.pdf )
42
Some Recommendations of the International
Conference on Nano-technology and Life Cycle
Assessment, Washington DC, 2-3 October 2006

• Do not wait to have near-perfect data
• Be modest about uncertainties clearly state
  relevant uncertainty aspects and assumptions
• Draw conclusions in the case of major or
  significant improvements otherwise, state that
  the nanoproduct and the conventional product are
  equivalent
• At this early stage, target estimates in the
  direction of protecting humans and the
• environment
• Separate the category indicators, grouping them
  by relevance/uncertainty
• Take care about overselling the benefits of the
  new nanoproduct, since assessment
• methodologies will improve and might show
  problems in the future
• Work with toxicologists and other scientists
  (geographical and socio-economic
• impacts) to review data and bound the issue
• Make data available for future LCA comparisons
  at the highest disaggregation level that
• is acceptable from a confidentiality
  perspective at a disaggregation level that is
• compatible with data availability (in terms of
  breakdown of processes) and
• as disaggregated as possible for further
  applications in assessment and
• Include explanations of assumptions and
  approaches.

http//www.nanotechproject.org/111/32007-life-cycl
e-assessment-essential-to-nanotech-commercial-deve
lopment ( NanoLCA.pdf )
43
Nanotechnologies and the Workplace
44
NIOSH (National Institute for Occupational Safety
and Health) is attempting to formulate workplace
safety standards
The goals for NIOSHs NTRC (Nanotechnology
Research Center) are as follows 1. Determine if
nanoparticles and nanomaterials pose risks for
work-related injuries and illnesses. 2. Conduct
research on the application of nanotechnology for
the prevention of work-related injuries and
illnesses. 3. Promote healthy workplaces through
interventions, recommendations, and capacity
building. 4. Enhance global workplace safety and
health through national and international collabor
ations on nanotechnology research and guidance.
http//www.cdc.gov/niosh/docs/2007-123/pdfs/2007-1
23.pdf
45
Protecting Workers in the Workplace
Increasingly US workers will find themselves
handling nanomaterials in the workplace.
Appropriate protection standards must be put in
place to insure their safety.
http//www.cdc.gov/niosh/docs/2007-123/pdfs/2007-1
23.pdf
46
Assessing Hazards in the Workplace
http//www.cdc.gov/niosh/docs/2007-123/pdfs/2007-1
23.pdf
47
Establishing a Nanotechnology Safety System
http//www.cdc.gov/niosh/docs/2007-123/pdfs/2007-1
23.pdf
48
Important question Can nanomedical systems be
bionanomanufactured under GMP principles?
49
Our MCF Team and Current Collaborators
Molecular Cytometry Facility Director James
Leary Lisa Reece (SVM) flow cytometry/
BioMEMS tissue culture Christy Cooper (SVM) -
bioanalytical chemistry, nanochemistry, XPS,
AFM Meggie Grafton (BME) - BioMEMS Emily Haglund
(BME) multilayered Qdots for ex-vivo
nanomedicine Mary-Margaret Seale-Goldsmith (BME)
multi-layered magnetic nanomedical systems
Michael Zordan (BME) prostate cancer, rare
cell flow/image cytometry Trisha Eustaquio (BME)
gene silencing/therapy interactive
imaging Jaehong Key (BME)- 3D/MRI imaging
Nanochemistry Don Bergstrom (Purdue)
X-ray Photon Spectroscopy Dmitry Zemlyanov
(Purdue)
High-Energy TEM Eric Stach (Purdue) Dmitri
Zakharov (Purdue)
Combinatorial chemistry/ Drug Discovery David
Gorenstein (UTMB) Xianbin Yang (UTMB) Andy
Ellington (UT-Austin)
Atomic Force Microscopy Helen McNally (Purdue)
Nanoparticle technology Nick Kotov (Univ.
Michigan) Kinam Park (Purdue) Alex Wei (Purdue)
Systems Biology Doraiswami Ramkrishna
(Purdue) Ann Rundell (Purdue) Robert Hannemann
(Purdue)
Nanotoxicity studies Debbie Knapp (Purdue) James
Klaunig (IU-SOM)
Magnetic Cell Sorting Paul Todd (SHOT, Inc)
LEAP Interactive Imaging Fred Koller
(Cyntellect, Inc.)
MRI Imaging Tom Talvage (Purdue) Charles Bouman
(Purdue)
BioMEMS/Microfluidics Rashid Bashir
(Purdue) Cagri Savran (Purdue) Kinam Park
(Purdue) Pedro Irazoqui (Purdue) Huw Summers
(Cardiff Univ, UK)
Nanomedicine studies Debbie Knapp
(Purdue) Deepika Dhawan (Purdue) Sophie Lelievre
(Purdue) Gerald Lutty (Johns Hopkins U) Tarl Prow
(U. Brisbane, Australia)
Image/confocal/SPR Paul Robinson (Purdue) Joseph
Irudayaraj (Purdue)
Funding from NIH, NASA, and Army Breast Cancer
Program
50
A Few Relevant Recent References

• Prow, TW, Salazar, JH, Rose, WA, Smith, JN,
  Reece, LM, Fontenot, AA, Wang, N, Lloyd, RS,
  Leary, JF "Nanomedicine nanoparticles,
  molecular biosensors and targeted gene/drug
  delivery for combined single-cell diagnostics and
  therapeutics" Proc. SPIE 5318 1-11, 2004.
• Prow, TW, Kotov, NA, Lvov, YM, Rijnbrand, R,
  Leary, JF Nanoparticles, Molecular Biosensors,
  and Multispectral Confocal Microscopy Journal of
  Molecular Histology, Vol. 35, No.6, pp. 555-564,
  2004.
• Prow, TW, Rose, WA, Wang, N, Reece, LM, Lvov, Y,
  Leary, JF "Biosensor-Controlled Gene
  Therapy/Drug Delivery with Nanoparticles for
  Nanomedicine" Proc. of SPIE 5692 199 208,
  2005.
• Prow, TW, Grebe, R, Merges, C, Smith, JN, McLeod,
  DS, Leary, JF, Lutty, GA "Novel therapeutic gene
  regulation by genetic biosensor tethered to
  magnetic nanoparticles for the detection and
  treatment of retinopathy of prematurity"
  Molecular Vision 12 616-625, 2006
• Prow, TW, Smith, JN, Grebe, R, Salazar, JH, Wang,
  N, Kotov, N, Lutty, G, Leary, JF "Construction,
  Gene Delivery, and Expression of DNA Tethered
  Nanoparticles" Molecular Vision 12 606-615, 2006
  
• Seale, M., Haglund, E., Cooper, C.L., Reece,
  L.M., Leary, J.F. "Design of programmable
• multilayered nanoparticles with in situ
  manufacture of therapeutic genes for
  nanomedicine"
• Proc. SPIE 6430 643003-1-7, 2007.
• Seale, M., Zemlyanov, D., Cooper, C.L., Haglund,
  E., Prow, T.W., Reece, L.M., Leary,
• J.F. Multifunctional nanoparticles for
  drug/gene delivery in nanomedicine Proc. SPIE
  6447
• 64470E-1-9, 2007.
• Leary, J.F. and Prow, T.W. Multilayered
  Nanomedicine Delivery System and Method
• PCT/US05/06692 on 3/4/2005.

51
Nanotoxicity References Chana, W-H, Nion-Shiao,
N-H, Pin-Zhen Lu, P-Z. CdSe quantum dots induce
apoptosis in human neuroblastoma cells via
mitochondrial-dependent pathways and inhibition
of survival signals. Toxicol. Lett. (2006),
doi10.1016/j.toxlet.2006.09.007 Darzynkiewicz Z,
Juan G, Li X, Gorczyca W, Murakami T, Traganos F.
Cytometry in cell necrobiology analysis of
apoptosis and accidental cell death (necrosis).
Cytometry. 1997 Jan 127(1)1-20. Kirchner,C.
Liedl, T., Kudera, S., Pellegrino,T., Munoz
Javier, A., Hermann E. Gaub,H.E., Stolzle,S.,
N. Fertig, Parak, W.P., Cytotoxicity of Colloidal
CdSe and CdSe/ZnS Nanoparticles. Nano Lett.,
Vol. 5, No. 2, 331-338, 2005. Oberdörster,G.,
Oberdörster, E. Oberdörster, J. Nanotoxicology
An Emerging Discipline Evolving from Studies of
Ultrafine Particles. Environmental Health
Perspectives 113(7) 2005 Ryman-Rasmussen,
J.P., Riviere, J.E.,Monteiro-Riviere, N.A.
Surface Coatings Determine Cytotoxicity and
Irritation Potential of Quantum Dot Nanoparticles
in Epidermal Keratinocytes. Journal of
Investigative Dermatology. 10 August 2006
doi10.1038/sj.jid.5700508 Shiohara, A., Hoshino,
A., Hanaki, K., Suzuki, K., Yamamoto, K. On the
cytotoxicity caused by quantum dots. Microbiol.
Immunol. 48(9) 669-675, 2004.
52
Some References on Nanotechnology Society
Nanotechnology Bibliography Mihail C. Roco,
William Sims Bainbridge, Societal Implications
of Nanoscience and Nanotechnology By, National
Science and Technology Council (U.S.).
Subcommittee on Nanoscale Science, Engineering,
and Technology (http//books.google.com/books?hle
nlrid4S54FQKgeQUCoifndpgRA1-PR5dqNanotec
hnologyscientificbooksotsjx6Ukw3Gqzsig82AEiQ
9PqEfuOew9OsPTl0wPc1kPPP1,M1 David M. Berube,
The Rhetoric of Nanotechnology In D. Baird, A.
Nordmann J. Schummer (eds.), Discovering the
Nanoscale, Amsterdam IOS Press, 2004. ISBN
1-58603-467-7 (http//cms.ifs.tu-darmstadt.de/fil
eadmin/phil/nano/berube.pdf ) David M. Berube,
NANO-HYPE, (foreword by Mihail C. Roco)
Prometheus Books, Amherst, NY 2005 ISBN
1-59102-351-3 (http//www.prometheusbooks.com)
Wade L. Robinson, Nano-Ethics In D. Baird,
A. Nordmann J. Schummer (eds.), Discovering the
Nanoscale, Amsterdam IOS Press, 2004. ISBN
1-58603-467-7 (http//cms.ifs.tu-darmstadt.de/fil
eadmin/phil/nano/robison.pdf ) James Moor and
John Weckert, Nanoethics Assessing the
Nanoscale from an Ethical Point of View In D.
Baird, A. Nordmann J. Schummer (eds.),
Discovering the Nanoscale, Amsterdam IOS Press,
2004.
53
Some References on Nanotechnology Society
Nanotechnology Bibliography Mihail C. Roco,
William Sims Bainbridge, Societal Implications
of Nanoscience and Nanotechnology By, National
Science and Technology Council (U.S.).
Subcommittee on Nanoscale Science, Engineering,
and Technology (http//books.google.com/books?hle
nlrid4S54FQKgeQUCoifndpgRA1-PR5dqNanotec
hnologyscientificbooksotsjx6Ukw3Gqzsig82AEiQ
9PqEfuOew9OsPTl0wPc1kPPP1,M1 David M. Berube,
The Rhetoric of Nanotechnology In D. Baird, A.
Nordmann J. Schummer (eds.), Discovering the
Nanoscale, Amsterdam IOS Press, 2004. ISBN
1-58603-467-7 (http//cms.ifs.tu-darmstadt.de/fil
eadmin/phil/nano/berube.pdf ) David M. Berube,
NANO-HYPE, (foreword by Mihail C. Roco)
Prometheus Books, Amherst, NY 2005 ISBN
1-59102-351-3 (http//www.prometheusbooks.com)
Wade L. Robinson, Nano-Ethics In D. Baird,
A. Nordmann J. Schummer (eds.), Discovering the
Nanoscale, Amsterdam IOS Press, 2004. ISBN
1-58603-467-7 (http//cms.ifs.tu-darmstadt.de/fil
eadmin/phil/nano/robison.pdf ) James Moor and
John Weckert, Nanoethics Assessing the
Nanoscale from an Ethical Point of View In D.
Baird, A. Nordmann J. Schummer (eds.),
Discovering the Nanoscale, Amsterdam IOS Press,
2004.
54
More References on Nanotechnology Society
ISBN 1-58603-467-7 (http//cms.ifs.tu-darmstadt.d
e/fileadmin/phil/nano/moor-weckert.pdf ) Jody A.
Roberts, Deciding the Future of
Nanotechnologies Legal Perspectives on Issues of
Democracy and Technology In D. Baird, A.
Nordmann J. Schummer (eds.), Discovering the
Nanoscale, Amsterdam IOS Press, 2004. ISBN
1-58603-467-7 (http// www.ifs.tu-darmstadt.de/fil
eadmin/phil/nano/roberts.pdf ) Emmanuelle
Schuler, Perception of Risks and Nanotechnology
In D. Baird, A. Nordmann J. Schummer (eds.),
Discovering the Nanoscale, Amsterdam IOS Press,
2004. ISBN 1-58603-467-7 ( http//
www.ifs.tu-darmstadt.de/fileadmin/phil/nano/schule
r.pdf ) Jurgen Altmann and Mark A. Gubrud,
Military, Arms Control, and Security Aspects of
Nanotechnology In D. Baird, A. Nordmann J.
Schummer (eds.), Discovering the Nanoscale,
Amsterdam IOS Press, 2004. ISBN 1-58603-467-7
(http//www.ifs.tu-darmstadt.de/fileadmin/phil/na
no/altmann-gubrud.pdf ) Ann Johnson, The End of
Pure Science Science Policy forom Bayh-Dole to
the NNI In D. Baird, A. Nordmann J. Schummer
(eds.), Discovering the Nanoscale, Amsterdam IOS
Press, 2004. ISBN 1-58603-467-7 (
http//www.ifs.tu-darmstadt.de/fileadmin/phil/nano
/johnson.pdf )
55
More References on Nanotechnology Society
Woodrow Wilson Project on Emerging
Nanotechnologies ( http//www.nanotechproject.org
/index.php?id44 ) UNESCO Bulletin The Ethics
and Politics of Nanotechnology (
http//unesdoc.unesco.org/images/0014/001459/14595
1e.pdf ) Nanotechnology and Life Cycle
Assessment A Systems Approach to Nanotechnology
and the Environment ( http//www.nanotechproject.o
rg/111/32007-life-cycle-assessment-essential-to-na
notech-commercial-development ) U.S. Army has
'big plans' for nanotechnology(MITs Institute
for Soldier Nanotechnologies) (http//www.smalltim
es.com/Articles/Article_Display.cfm?ARTICLE_ID268
741p109) Janine M. Benyus. Biomimicry
Innovation Inspired by Nature, New York William
Morrow. Co., 1997, 308 pp., ISBN
0-688-13691-5 Aspen Ideas Festival- Interview
with Janine Benyus (http//www.aspeninstitute.org
/atf/cf/7BDEB6F227-659B-4EC8-8F84-8DF23CA704F57D
/Transcript_Biomimicry.pdf )
56
Thanks for your attention!