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Nanospheres
and Nanoparticles in Advanced Life Science Applications |
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Ed Wijaranakula, Ph.D.
Chief Technical Officer, Infotix
Systems, Inc. - June 30, 2004
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During
the past few years, new and innovative developments of
nanospheres and nanoparticles for drug delivery systems
and life science applications have been reported [1-2].
This new
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technology has raised a great deal of attention
from both scientists and investors, since it promises
several new low-cost therapeutic treatments and diagnostics
which are non-invasive, highly sensitive and precise.
An
important issue, particularly in human therapeutic
treatments that require in-depth understanding before
investing in the nanoparticle-based companies, is the
capability of controlling the size distribution of nanospheres and nanoparticles.
One critical criteria, for example, is based upon the
fact that the smallest blood vessels, the
capillaries, are
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approximately 8 microns in diameter and hence no more than 1000 particles per ml over 2
microns in an intravenous injection is recommended to
prevent clotting [3]. The nanoparticles should be
designed such that they are stable enough to withstand
the harsh conditions of the bloodstream or are not filtered
out by the kidneys as they are considered to be foreign
to the body. In this report, we provide some
insight on new
potential products and advanced applications based upon
nanospheres and nanoparticles.
Non-Invasive
Stroke Therapy:
According to the American Society
of Cardiovascular & Interventional Radiology, more
than 500,000 people suffer strokes every year and
stroke is the third leading cause of death. Currently,
catheter-based brain interventions, including invasive
catheter placement into the brain artery and intravenous
injection of the tissue plasminogen activator (t-PA) to the
clot site, is the
only FDA-approved clot-busting therapy for
treating strokes.
Research scientists at Argonne National Laboratory are
in the conceptual development stage of a non-invasive
acute stroke treatment based on nanotechnology using
magnetically guided encapsulated nanoparticles [4].
The drug delivery concept consists of injecting a small
dose of "designer" magnetic particles, containing active t-PA into the vein, which
are then
magnetically guided and trapped at the blood clot site
by an externally applied magnetic field. The drug is then
released from the particle matrix using focused
ultrasonics.
The particle matrix, which is a mixture of non-toxic
biodegradable magnetic metal oxide nanophases (i.e. Fe3O4
or γ -Fe2O3) and active t-PA, is
packed in biodegradable poly(lactic acid) (PLA)
nanospheres having sizes ranging from 100 nm to several
microns. PLA nanospheres are encapsulated with poly(ethylene glycol) (PEG) to
provide protection
against interaction with the patient's immune system.
White blood cells can attack the nanoparticles and
reduce their circulating life in the blood stream.
For years, biotech companies, such as Enzon Pharmaceuticals
(NASDAQ : ENZN), Maxygen (NASDAQ : MAXY) and
venture-backed Novocell, Inc., have developed PEG technology
(pegylation). Pegylation can involve the attachment of PEG to therapeutic proteins or small molecules,
such as cancer chemotherapy agents and antibiotics, or PEG encapsulation of individual cells and cell
clusters. |
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Nanoparticle DNA Probe: The widely used DNA probe,
using techniques such as the fluorophore-enhanced polymerase chain
reaction (PCR) and a gene chip microarray to identify a
segment of unknown DNA strands, has a wide range of
applications in life sciences, medicine, bio-defense and
genomic research. In 2003 alone, Affymetrix (NASDAQ :
AFFX), one of the leading manufacturers of gene chips, sold over $300 million of its GeneChip system and
other products directly to customers, including Schering
AG (NYSE ADR : SHR), Amgen (NASDAQ: AMGN), and Roche. Nanotech start-ups such as Northbrook, IL-based
Nanosphere,
Inc., is developing a nano-scale DNA probe using gold
nanoparticles, having sizes as small as 13nm in diameter.
These nanoparticles are attached
with hundreds of complementary DNA sequences designed to
capture specific genomic targets from a clinical sample.
Captured DNA strands are isolated and analyzed using Nanosphere's proprietary molecular detection system and
data analysis software. Because the
probe is at nano-scale, its sensitivity could reach
a
level of 10,000
times greater than the current fluorophore-enhanced PCR
technique.
In the past two years,
Nanosphere, Inc. received third-round financing for
a total of $15 million from Lurie
Investments, NextGen Partners LLC, Kyoto, Japan-based
Takara Bio Inc. and a $2.5 million U.S. Government
contract for the identification of biological toxins.
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Nano-Scale Cancer Treatments: With a goal of
reducing the unpleasant side effects for patients that
are associated with chemotherapeutic treatments, government, academia and
industry are
developing several alternative, safe and effective cancer
therapies including anti-angiogenesis and novel non-invasive thermotherapies such as Nanoshell optical
therapeutics [5] and the Targeted Nano-Therapeutics™ (TNT™)
system.
Research scientists at a Houston, Texas-based
Nanospectra Biosciences Inc. and Rice University are in early-stage development of
novel "Nanoshell"
optical therapeutics. This unique therapy employs "Nanoshells",
having sizes ~ 100nm, made of silica nanospheres coated
with an ultra-thin gold layer. The "Nanoshells"
are conjugated with antibodies so that
they seek out and bind themselves to the cancer
cells when the solution is intravenously injected to the cancer patient.
Near-infrared light (laser) is applied externally to the
diseased cells bound with the "Nanoshells"
through the tissue. A solid-state interaction between gold
and laser generates heat at the "Nanoshells" which
in turn destroys the cancer cells. Nanospectra Biosciences
just received $3 million funding from the U.S. Government to develop nanoshells for
breast cancer
treatment.
Based upon similar thermotherapeutic approaches, Triton
BioSystems, Inc., a Chelmsford, MA-based venture-backed
company, is developing non-invasive targeted therapeutics
that also use heat to treat late-stage breast, lung, colon,
pancreatic and prostate cancers. The Triton BioSystems
Targeted Nano-Therapeutics™ (TNT™) System is an
injectable product that uses nanoscale magnetic spheres made
of a special formulated material that
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when activated by
external magnetic energy, generates localized heat and
destroys cancer cells. According to, Mr. Samuel Straface,
Triton BioSyStems CEO, at temperatures exceeding 42°C,
cancer cells which are more sensitive to heat than normal
cells, are destroyed [6]. Since
the spheres are so small, the heating is very local and does
not harm the healthy vital tissues or organs nearby, unlike
chemotherapy or radiation. The company is in pre-clinical
development and in 2006, is anticipated to begin human
clinical trials.
REFERENCES
[1]
M.R. Kumar, J Pharm Pharmaceut Sci, 3(2):234-258, 2000.
[2] S. Rudershausen, et al , European Cells and Materials Vol. 3. Suppl. 2, 2002:
81-83.
[3] Limit Test For Particulate Matter. British Pharmacoepia 1993, Volume 2, Appendix X111. London, HMSO.
[4] M.D. Kaminski, et
al, Using Nanoscale Technology to Help Stroke Victims: Prototype Nanoparticles for Future Magnetically Guided, Targeted Tissue Plasminogen Activator Stroke Therapy,
Argonne
News,
April 23, 2004.
[5] C. Loo, et al, Technol Cancer Res Treat. 2004 Feb;3(1):33-40.
[6] Nanoparticle News, December 2002.
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About
NMS Research Analysis:
NMS Research Analysis is a service of Infotix Systems, offering
in-depth research analysis of high-tech companies and emerging
technology in sectors ranging from semiconductors, biotech,
nanotechnology, IT hardware and data storage to wireless, Internet
and consumer electronics. Dr.
Wijaranakula holds
a long
position
or control in ENZN.
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