NANoPArtICLES IN Food bacteria synthesize iron oxide nanoparticles and use them to orient themselves...
Transcript of NANoPArtICLES IN Food bacteria synthesize iron oxide nanoparticles and use them to orient themselves...
ISSUE 24 MAY 2012 ISSN 1757-2517
Plus the latest & best news on nano for industry, society & the environment
THE MAGAZINE FOR SMALL SCIENCE
NANoPArtICLES
IN Food- NATuRE’S bARRIERS pROTEcT
Magnetic Hyperthermia for CancerAdvances in magnetic nanoparticles offer more effective ways to treat brain, pancreatic and prostate cancers.
Porous Silicon – revolutionising drug targeting & delivery Nanocarrier-mediated drug delivery systems are one of the most attractive applications of nanomedicine.
Nanoparticles in Food: close but not too close.Skin and mucosae pose barriers to the entry of nanoparticles into the human body.
Nanotechnologies for Soldier Enhancement, Protection & SupportA case study in portable Energy Generation, Storage and Management for Field Troops.
FEATURE
These bacteria synthesize iron oxide
nanoparticles and use them to orient
themselves in the earth’s magnetic field.
These nanoparticles are in the size
range 20-70 nm and have an impressive
crystallographic quality and display
heating power values which have not yet
been reached by chemically-synthesized
iron oxide ones. Recent results obtained
by a French team led by E. Alphandery
shows that these nanoparticles are more
efficient in destroying tumours grafted
on mice than their artificial counterparts.
This is not only due to their large heating
power, but also to their better ability to
penetrate the cells.
If one wants to reach larger heating
power values, a change in the nature of
the nanoparticles is required. Indeed,
the maximum heating power value is
directly proportional to the saturation
magnetization of the material used.
Iron oxides are not the best material for
this and magnetic materials composed
only of the ‘3d elements’ (Fe, co, Ni)
and their alloys, display a saturation
magnetization which can be more than
twice that of iron oxide. However, co
and Ni are known to be toxic and could
not of course be injected into humans.
This explains why our group has
focused its efforts on iron nanoparticles.
Synthesizing monodisperse iron
nanoparticle of a controlled size is a
real challenge, which has been taken up
by the chemists of our laboratory. This
effort has been rewarded by the fact that
our nanoparticles present the largest
heating power of any in the literature
so far. However, the use of iron needs
to address two important questions.
The first one concerns the protection of
these nanoparticles against oxidation
once inside the body, which requires
synthesizing an efficient protecting core.
The second concerns the toxicity: if
iron is not intrinsically toxic to humans,
the effect of injecting metallic iron, a
potential reducing agent, into the body
still raises the toxicity question.
Other medical applications of magnetic nanoparticlesIn addition to magnetic hyperthermia,
magnetic nanoparticles could be
used in several other approaches in
nanomedicine. For instance, a San Diego
team conducted by S. Jin has synthesized
nanocapsules containing both a drug and
magnetic nanoparticles. They have shown
that when they heat the nanoparticles
using the same principle as the one used
in magnetic hyperthermia, the increase
of temperature stimulates the release of
drugs out of the nanocapsule. This could
be used to release drugs very locally
inside the tumours and thus minimize
secondary effects during treatments.
Another advantage of combining drugs
and magnetic nanoparticles is drug
targeting, since the particles can be
guided or accumulated into a region of
interest using external static magnetic
fields.
Revolutionising Drug Targeting and Delivery
Putting a piece of ferromagnetic magnetic material into an alternative magnetic field increases its temperature in two different ways.
The first way is that the magnetization of the magnetic
material will try to follow the magnetic field variations
and to keep in alignment with it, but will do it with a
lag, conducting to a hysteresis loop. The area of this
hysteresis loop corresponds to irreversible energy losses
which are released by the magnetic nanoparticles, heating
its surrounding. Let’s call this phenomenon “heating by
hysteresis losses.”
The second way is due to the combination of two well-
known laws of the physics: Faraday’s law and Ohm’s law.
The first one stipulates that when any material is submitted
to a varying magnetic field, an electrical current is induced
into the material to try to compensate the magnetic field
variation (these currents are called by the French Foucault
currents and by the rest of the world as eddy currents!).
These circulating currents heat the material by the Ohm’s
law and are thus limited in resistive materials, but very
present in metals. Eddy currents are strongly enhanced in
ferromagnetic metals compared to non-magnetic ones since
the reversal of the magnetization by the external magnetic
field is equivalent to a gigantic change of magnetic field
inside a ferromagnetic material. For a given material, the
respective importance of the heating by hysteresis losses
compared to the heating by eddy currents depends on the
size of the piece of material put into the magnetic field. For
a large piece of material, eddy currents dominate. Thus,
they are the ones which mainly heat the pot (which needs
to have a ferromagnetic iron bottom) put on an induction
plate.
Note that the frequency and amplitude of the magnetic field
used in an induction plate are very similar to the ones used
in magnetic hyperthermia. On the contrary, if a nanoparticle
is put into the magnetic field, eddy current are very limited
and the only sources of heat are the hysteresis losses.
Finally….
All progress in these fields is only
possible with close collaboration
between various scientists:
physicists to predict, measure
and explain hyperthermia
experiments; chemists and bio-
chemists to synthesize high-
quality functionalized nano-
particles; biologists to perform
toxicity and efficiency assays
on cells and animals; engineers
to develop the hyperthermia
equipment adapted to humans,
and physicians to perform
clinical trials. Nowadays, many
major scientific advances are the
product of a large community
of collaborating scientists, and
nanomedicine is, in that sense,
a good example of the beauty of
modern collaborative science.
*At the Laboratoire de physique et chimie des Nano-Objets, Toulouse, France (http://lpcno.insa-toulouse.fr), researchers have been working on the properties of magnetic nanoparticles. Since 2005, several members of the laboratory have been working on the optimisation of nanoparticles for magnetic hyperthermia. Their work is funded by the Midi-pyrénées Region and by the InNabioSanté foundation.
By Hélder A. Santos, Division of Pharmaceutical Technology, Faculty of Pharmacy, University of Helsinki, Finland
Nanomedicine and drug nanocarriersOne of the biggest challenges in the modern world is to find healthcare solutions that
can fully benefit humankind. This means that scientists are expected to come up with
great ideas and develop tools that can be applied to the diagnosis and treatment of
diseases, such as cancer. In this respect, considerable attention has been focused on
the field of nanomedicine. Nanomedicine makes use of nanoparticles (structures with
at least one dimension bellow 100 nanometers), as offering new solutions to previously
insoluble medical problems and proposing new therapies.
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FEATURE
Porous Silicon -
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FEATURE FEATURE
In recent years, a great variety of
nanotechnology based platforms have
been developed and employed to
improve the delivery of therapeutics
to the disease site. currently, the
nanoparticles used in the clinic, and
the majority of nano-therapeutics
/ diagnostics under investigation,
accommodate single- or multiple-
functionalities on the same entity.
The biological barriers are very
heterogeneous which may prevent
the therapeutic and imaging agents
from reaching their intended targets
in sufficient concentrations. Therefore,
there is an emerging requirement to
develop multimodular nanoassemblies
in which different components
with specific functions may act in a
synergistic manner.
unfavourable physicochemical properties
of many drug molecules may affect their
bioavailability and, consequently, affect
their therapeutic efficacy and efficiency.
In the past, researchers have struggled
to develop advanced drug delivery
systems for controllable and enhanced
drug release, as well as for targeted drug
delivery. In this context, nanocarrier-
mediated drug delivery systems are one
of the most attractive applications of the
emerging nanomedicine field. Targeted
and controlled drug delivery systems
improve drug bioavailability, as well as
their pharmacological and therapeutic
properties, while minimizing collateral
effects.
The pharmaceutical industry has been
increasing funding for research in the
development of advanced drug delivery
systems with investments of $131.6
billion in 2010, estimated to increase
in 2016 to $175.6 billion (http://www.
bccresearch.com/report/advanced-drug-
delivery-systems-phm006h.html).
The birth of nanostructured pSi for the biomedical world The element silicon (Si) is a tetravalent
metalloid , and the second most
abundant element (after oxygen) in the
Earth’s crust, representing about 25.7%
of it by mass. Si very rarely occurs as the
pure free element in nature, but is more
widely distributed in various forms as
silicon dioxide (silica), SiO2, or silicates.
The great boost for the research on
porous silicon (pSi) occurred when
in 1989 Leigh canham revealed the
potential of nano-engineered Si as a
semiconductor while working at the
Defence Research Agency (now QinetiQ)
in Malvern, uK. canham explored the
various practical uses of the luminescent
properties of the pSi materials. However,
the great breakthrough occurred in
1995 when canham demonstrated that
pSi materials were both biodegradable
and biocompatible (non-toxic), and
thus, could be safely adsorbed and
eliminated by the body after it has been
nano-engineered (canham 1997). This
brilliant discovery led to groundbreaking
achievements in the biomedical field
ever since.
because the nanostrcutured Si
materials were both luminescent
and biodegradable opened a world of
possibilities for the versatility of the
material in applications in biosensing,
pharmaceuticals, biomedicine and the
food industry. Regarding the biomedical
applications, there is today an increasing
interest in using pSi materials as carriers
for controlled drug delivery, targeted
cancer therapy, medical imaging, tissue
engineering and improved health and
beauty products.
The properties of nanostructured pSi materialspSi, often designated as mesoporous
silicon, is a material with a honeycomb
structure containing pores with
diameters between 2 and 50 nm, and
sometimes referred to as nanoporous
to emphasize its nanoscale size nature.
These pores can be filled with drugs,
peptides, genes, proteins, radionuclides
and other therapeutics or vaccines. The
most extraordinary properties of these
materials are their large surface area
(200–500 m2/g), porosity (50–80%) and
large pore volume (0.5–2.0 cm3/g), which
can act as reservoirs for storing drug
molecules for drug delivery applications.
The pore diameters of pSi can be
tuned allowing for the loading of
various therapeutic compounds. Due
to the stable and rigid framework of
pSi materials, it makes therapeutic
compounds resistant to mechanical
stress, pH, and fast degradation when in
the body. In this context, the interest and
the applicability of pSi-based materials
is increasing due to its potential to
revolutionize the biomedical field, in
particular as drug delivery carriers
or implantable devices. pSi materials
(micro- and nanoparticles) have well-
defined structures and surfaces, and they
are also chemically inert and thermally
stable.
Nanostructured pSi materials are
produced typically from Si wafers via
electrochemical etching, where the
control of the nano-enginered structures
is possible. These nanostructures are
stable under the harsh conditions of
the stomach and gastrointestinal (GI)
lumen. by fine-tuning the porosity of
the pSi materials it is possible to make
it degradable in the body. For example,
nanostructured pSi with porosities >70%
dissolves in all simulated body fluids
(except gastric fluids), whereas pSi with
porosities <70% is bioactive and slowly
biodegradable.
In addition to that, pSi exhibits a number
of properties that make it an attractive
material for controlled drug delivery
applications (Figure 1). For example,
the electrochemical production allows
the construction of tailored pore sizes
and volumes that are controllable from
the scale of microns to nanometers.
A number of convenient chemistries
exist for the modification of pSi surfaces
that can be used to control the amount,
identity, and in vitro/vivo release rate of
therapeutic payloads. Another important
feature of pSi is that in the body it
degrades into silicic acid, [Si(OH)4], which
is the most natural form of Si in the
environment, non-toxic, important in
human physiology in protecting against
aluminium toxic effects, and is efficiently
excreted by the kidneys. Si is also an
essential nutrient for the human body
and in the Western world the average
daily dietary intake of Si is about 20−50
mg/day. A major source of Si intake
comes from beer.
How nanostructured pSi can revolutionary the healthcare?The pharmaceutical industry faces
great challenges in the development of
therapeutic compounds that are both
efficient for the treatment of the disease
in question, with minor side effects.
However, in most cases this cannot be
achieved, particularly because many
drug molecules administrated orally
suffer from poor bioavailability, i.e. they
are poorly soluble with low dissolution
rates in the intestinal lumen, as well as
suffering from poor permeability across
the GI wall. Furthermore, cytostatic drug
compounds usually lead to very adverse
side effects after administration.
Due to the properties of nanostructured
pSi materials, the most challenging
drug compounds can be loaded into
nanoporous pSi in order to overcome
the abovementioned problems. because
the drug molecules are confined inside
the pores, usually not much larger
than the drug molecules themselves,
their physicochemical properties can
be enhanced (Salonen et al., 2008). This
ensures that the therapeutic compounds
carried by the pSi materials will be
released from the pores efficiently in
a controlled manner, so that they are
pharmacologically active with very
minimal side effects to the patients. This
enables the control and local release
of the drug where its action is required
and simultaneously controls the drug
concentration in the blood.
Scientists have successfully loaded a
large variety of therapeutic compounds
into the nanopores of pSi materials, and
their release properties have extensively
been studied in the literature mainly
for oral drug delivery applications, but
also for other routes of administration,
such as intravenous (Santos et al., 2011).
Similarly, peptide or protein molecules
have also been successfully loaded into
nanostructured pSi or attached to its
surface, and their efficient sustained /
fast release and activity evaluated. This
is particularly interesting because many
peptides or proteins, such as insulin for
diabetes, have to be administrated as
solutions or suspensions frequently as
injections, due to the short duration of
action of the peptides in vivo, as well
as due to their rapid degradation and
elimination from the blood circulation.
Recent research has demonstrated that
nanostructured pSi carriers containing
food or water intake regulating peptides
could prolong the effect of the peptide,
which could reduce the frequency of
injections to the patients in the future,
or even be administrated via other route,
e.g. orally.
Other application of pSi materials is in
ocular therapy. Scientists have employed
nanostructured pSi-based technology
to delivery drug compounds inside the
eye of rabbits in order to minimize the
invasiveness of the treatments, with
controllable and monitorable drug
delivery concentrations enabling long-
acting local treatment of intraocular
diseases, which could help in the future
patients with problems in the retina and
choroid.
Another very important and more
recent application of nanostructured
pSi materials is in targeted delivery
for cancer therapy. Targeted and
controlled drug delivery also improves
drug bioavailability, as well as the
pharmacological and the drug
therapeutic properties, minimizing
detrimental adverse effects. The large
number of defense mechanisms in the
body prevents injected foreign agents
such as chemicals, biopharmaceutics,
and nanostructures from homing in to
their intended destinations. Therefore,
more sophisticated nanocarriers need to
be developed and tested.
Targeted delivery systems are designed
to deliver the drug precisely to the body
sites where it is needed, in proximity to,
or inside a cell, and to release a desired
amount of drug over a controllable
period of time. In specific (targeted)
delivery, the surface of a nanocarrier
is often bio-functionalized with
biological recognition ligands loaded
with anticancer drug, and may also
contain simultaneously an imaging
agent (Figure 2). These multifunctional
properties make nanocarriers capable
of targeting cancer cells and, at the
same time, imaging the cancer and
deliver appropriate therapeutic drugs.
Another advantage of such an approach
is the accuracy of targeting and the
preservation of healthy tissue, without
compromising the patients’ health.
Taking this into account, a multistage
pSi-based system comprising several
nanocomponents or “stages” was also
developed (Goding et al., 2011). Stage 1
nanostructured pSi particles are designed
in a nonspherical geometry to enable
superior blood margination and increase
cell surface adhesion. The idea is to be
able to load the nanoparticles (so-called
Stage 2) and efficiently transport them
from the administration site to the
disease lesion. Stage 2 nanoparticles can
be any available nanoparticles such as
liposomes, micelles, inorganic/metallic
nanoparticles, etc., within the size
Figure 1: List of the most relevant properties of the nanostructured pSi nanocarriers: Si wafer and pSi powder-based microparticles (left); mesoporous structure (~ 10 nanometers) and pSi solution-based nanoparticles (right). Other properties emphasized are: the small pore sizes yet, large or small enough to allow a fast or slow drug release; the possibility to functionalize the surface of pSi materials for targeted therapy; the pSi nanocarriers can be hydrophilic (or hydrophobic) enhancing its wettability properties; considerable amounts of therapeutic compounds can be loaded inside the pSi nanopores; the nanostructured pSi fabrication can be fine-tuned to produce a certain surface chemistry, pore size and shape, and morphology of the material; due to its top-down manufacture approach, nanostructured pSi can be easily scaled-up.
FEATURE
References
range of 5−100 nanometers in diameter.
Such systems have been demonstrated
to efficiently act as nanocarriers for
magnetic resonance imaging contrast
agents and to efficiently deliver small
interfering RNA (siRNA) for cancer
therapy.
Although therapy is one of the most
promising applications of nanostructured
pSi materials, pSi has also great
potential in pre-diagnostics in imaging
applications. Due to its intrinsic
luminescence nanostructured pSi
materials can be imaged in the body
by, for example, near-infra-red imaging
techniques. Another advantage is that
the pSi surface is easily modified by
radiotracers, such as fluorine-18 (Santos
et al., 2011) and others, which can be
used in positron emission tomography
for clinical diagnostics and drug
development.
Figure 2: Schematic representation of a spherical-shaped nanostructured pSi nanocarrier and its potentialities in drug delivery, cancer therapy and bio-imaging: (i) first the therapeutic compounds (drug/peptide) are loaded into the pores of nanostructured pSi; (ii) the surface of pSi nanocarriers can then be modified (functionalized) with different biological ligands and polymers, labelled with fluorophores and/or radioactive isotopes for non-invasive imaging applications; the pSi nanocarriers can then travel in the bloodstream and release the therapeutic compounds in the vicinity of unhealthy cells or tissues and simultaneously provide a real-time monitoring of its actions.
SummaryNanostructured pSi-based materials have
many interesting properties that can be
useful for biomedical applications such
as detection, identification, imaging,
and delivery of therapeutics to tissues,
organs or cells of interest. The great
advantages of the nanostructured pSi
materials are the good biocompatibility,
biodegradability, high pore volume
necessary for hosting large amounts of
therapeutics, different pore sizes for fine
control of drug loads and release kinetics,
high surface area for drug adsorption,
easy surface chemistry modification for
further biofunctionalization and control
of drug loading and release.
The nanostructured pSi properties enable
it to dissolve in the body at a controlled
rate while releasing drugs over minutes,
hours, days, months, or even years.
After the loaded drug is released, all
that is left in the body is pure Si, which
dissolves into non-toxic silicic acid
and is safely excreted from the body.
Doctors have then a range of options for
introducing drug-loaded nanostructured
pSi materials into the body: orally, via
injection, transdermally, or with a patch,
implant or coating.
One can envisage that future
generations of nanostructured pSi-based
nanocarriers will effectively improve the
quality of life of patients by efficiently
transporting drugs to targeted areas
without damaging healthy cells. These
nanocarriers can be strictly designed
for the intent of their application, with
a proper response and, in the future,
also for the delivery of drug dosages
according to the clinical needs of the
patient and pathology. The versatility
of the nanostructured pSi platform and
its emerging properties will enable the
creation of personalized solutions with
broad clinical implications within and
beyond the realm of cancer theranostics.
This is because nanostructured pSi-
based materials have the capacity to
incorporate and take advantage of a
variety of existing, novel, or clinically
used, therapeutic and imaging agents
from a “nano-toolbox”, while enabling
synergistic application of these
nanotechnologies to form a higher
generation nanosystem in the future.
canham LT (1997). properties of porous silicon. London, Short Run press Ltd.
Salonen J, Kaukonen AM, Hirvonen J, Lehto V-p (2008). Mesoporous silicon in drug delivery applications. J. pharm. Sci. 97: 632−653.
Anglin EJ, cheng L, Freeman WR, Sailor MJ (2008). porous silicon in drug delivery devices and materials. Adv. Drug. Delivery Rev 60: 1266-1277.
Santos HA, bimbo LM, Lehto V-p, Airaksinen AJ, Salonen J, Hirvonen J (2011). Multifunctional porous silicon for therapeutic drug delivery and imaging. curr. Drug Discov. Tech. 8: 228-249.
Godin b, Tasciotti E, Liu X, Serda RE, Ferrari M (2011). Multistage nanovectors: from concept to novel imaging contrast agents and therapeutics. Acc. chem. Res. 44: 979–989.
Nanoparticles
in Food: close, but not too closeSkin and mucosae pose barriers to the entry of nanoparticles into the human body. Eleonore Fröhlich, Center for Medical Research, Medical University of Graz, and Eva Roblegg, Institute of Pharmaceutical Sciences, Karl-Franzens University, Graz.
FEATURE
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