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Silica Nanoparticles
Nano Bio Tech
Nano Bio Tech
www.aczonpharma.com
ACZON CUSTOM MADE
CUSTOM DESIGN OF INNOVATIVE
NANOPARTICLE-BASED TOOLS
OUR TECHNOLOGY
Aczon Silica NanoParticles are made up of spherical atomic or
molecular clusters, with diameter between 5 and 100 nm, and
consist of two structural compartments: Core and Shell.
They are made up of a Silicon-based polymer bonded to a
surfactant molecule. On the shell, NPs are functionalized with the conventional
functional groups (amino, carboxyl, etc.), or activated, for bioconjugations
by means of a crosslinker (maleimide); the core may be left empty or it may
contain fluorochromes or other molecules (linked, or otherwise, with a covalent
bond) for biotechnological or other kind of applications.
NanoParticles are used in the most extensive range of applications (diagnostic
and clinical applications, but also in the fields of biotechnology, chemistry,
pharmacy, agriculture, environment and other).
HOW THEY ARE MADE
The method used to produce Aczon NanoParticles is called the Micelle Assisted Method, which that includes the following phases (described and
schematized in brief):
1. The surfactant, the silanized PEG and/or Amino silanized PEG (for
functionalized NPs) are dissolved in water where they spontaneously form
micelles.
2. The silica precursor is hydrolyzed and condensed extensively until the
structures lock.
3. Purification is performed by means of dialysis and filtration.
ACZON
CUSTOM
MADE:
designed for
customer needs
Fig. Micelle-assisted
Method.
Main Features
Main Advantages
· total standard diameter of NPs:
20-25nm
· core diameter
(including molecules): 10 nm
· high solubility in aqueous
solutions
· remarkable monodispersity and
high chemical stability
· efficient spectral performances
· variable controlled size
· highly reproducible and
atoxic synthesis
· low handling of molecules linked in the Core
· outstanding chemical stability
and atoxicity
· excellent monodispersity
ACZON CUSTOM MADE
CUSTOM MADE FOR IN VITRO
DIAGNOSTICS
Recent years have unprecedented growth of research and
applications in the area of nanoscience and nanotechnology.
Anticipated applications in medicine include drug delivery,
both in vitro and in vivo diagnostics, nutraceuticals and
production of improved biocompatible materials. Engineered
nanoparticles are an important tool to realize a number of
these applications (A.4).
To provide a new nanomedicine platform for in vitro diagnostics, imaging,
detection and treatment, as well as building blocks for multifunctional
materials and different applications (A.2), it is extremely important to avail of
nanoparticles with variable controlled size. Each field of application requires
specific specifications; shape and dimensions are of great interest.
References A - Custom made for in vitro
diagnostics:
1- Smith J. E. et al., “Bioconjugated
silica-coated
nanoparticles
for
bioseparation
and
bioanalysis”.
Trends in Anal.Chem., 2006.
2- Huo Q.S. et al., “A new class of
silica cross-linked micellar core-shell
nanoparticles”, JACS, 2006.
3- Chan C. P. et al., “New Trends in
Immunoassays” Adv Biochem Engin/
Biotechnol, 2008.
4- De Jong W.H. et al., “Drug delivery
and nanoparticles: Applications and
hazards”, Int. J. of Nanomedicine,
2008.
5- Chan C. P. et al., “In vitro diagnostic
prospects of nanoparticles” Clin.
Chim.ACTA , 2009.
6- Arruebo M. et al., “AntibodyConjugated
Nanoparticles
for
Biomedical Applications”, J.Nanomat.,
2009.
A wide range of molecules/biomoieties can be conjugated to the nanoparticles
including low molecular weight ligands (folic acid, thiamine, dimercaptosuccinic
acid), peptides (RGD, LHRD, antigenic peptides, internalization peptides),
proteins (BSA, transferrin, antibodies, lectins, cytokines, fibrinogen, thrombin),
polysaccharides (hyaluronic acid, chitosan, dextran, oligosaccharides,
heparin), polyunsaturated fatty acids (palmitic acid, phospholipids), DNA,
plasmids, siRNA, miRNA, and so forth (A.6).
The figure below shows the conjugation of nanoparticles with antibodies; it
combines the properties of the nanoparticles themselves with the specific
and selective recognition ability of the antibodies toward antigens. Also, the
improvement in the cellular uptake as well as the major intracellular stability may
be two of the major advantages of using antibody conjugated nanoparticles
(A.6)
What antibodies can offer NPs and what NPs can offer to Abs
Antibodies
Nanoparticles
Specificity
Not Specific
Nano-size
Biological component
Recruits components of
the immune system
Can find specific target
Specific
Carriers
Can activate
the immune
system
Several proprieties
Thrmal, Magnetics, Imaging
Drug delivery-controlled
Many properties
Versatility
Why Aczon NanoParticles for in vitro diagnostics?
Aczon NanoParticles produced according to customer specifications are
created by including fluorescent and non-fluorescent molecules, functionalized
with different chemical groups and/or conjugated with proteins (such as
antibodies, or enzymes), peptides, nucleotide sequences and much more.
We can synthesize NPs incorporating special molecules of the customer and conjugate or
functionalize according to specific requests.
Fig. Advantages of
conjugating nanoparticles
with antibodies
(Arruebo M. et al., “AntibodyConjugated Nanoparticles
for Biomedical Applications”,
J.Nanomat., 2009).
ACZON CUSTOM MADE
CUSTOM MADE FOR IN VIVO DIAGNOSIS:
NanoTrackTM
The development of biomedical imaging techniques, such
as computed X-ray tomography (CT), optical imaging,
and magnetic resonance imaging (MRI), has brought
significant advances for diagnosis and therapy. Inorganic
nanoparticles are emerging as promising probes to shed
light on biological processes and diseases occurring at
molecular and cellular levels.
They have the potential to advance imaging from its current anatomy-based
level to the molecular level, so-called “molecular imaging”. Upon conjugation
with target-specific biomolecules, these tiny probes (1–100nm) can travel
through the human body in the blood and lymphatic vessels and they can
identify the desired target through specific biological interactions, such as
antibody–antigen, nucleic acid hybridization, and gene expression (B.1).
References B - Custom made for in vivo
diagnosis:
1- Young-wook J. et al., “Chemical
Design of Nanoparticle Probes
for
High-Performance
Magnetic
Resonance Imaging”, Angew. Chem.
Int., 2008.
2- Gagnon M.K.J. et al. “Highthroughput in vivo screening of
targeted molecular imaging agents”
PNAS., 2009.
3- Perrault S.D. et al. “In vivo assembly
of nanoparticles components to
improve targeted cancer imaging”
PNAS., 2010.
4- Pantazis P. “Second Harmonic
generating (SHG) nanoprobes for in
vivo imaging” PNAS., 2010.
5- Hwang D. W. et al., “Molecular
Imaging Using PET/MRI Particle”, The
Open Nuclear Med. J., 2010.
The development of efficient imaging probes has accelerated the possibility
to detect the grafted cell migration in vivo and evaluate drug response in
the molecular imaging field, offering repetitive imaging detection, signal
quantification and tomographic capabilities. Furthermore, the development
of multimodal imaging nanoprobes can present a multidisciplinary approach
for developing merged PET-MRI imaging devices, drug delivery and cancer
tracking (B.5).
The figure below shows a schematic nanoparticles assembly with contrast
agent in vivo. Gold nanoparticles stabilized with biotinylated PEG (denoted
as biotin-PEG anchor) are injected as a first step. These enter tumors through
leaky vasculature and passively accumulate in the extracellular matrix over
24 h. Fluorescently labelled streptavidin is injected, which leaks into tumors
and interacts with biotin on the gold nanoparticles in the interstitium. This
favourably alters the contrast agent’s tumor accumulation kinetics (B.3).
Fig. Schematic nanoparticle
assembling with contrast
agent in vivo (Perrault S.D.
et al. “In vivo assembly of
nanoparticles components
to improve targeted cancer
imaging” PNAS., 2010).
Why Aczon NanoParticles for in vivo diagnosis?
Aczon NanoParticles fit into this context and are designed for diagnostic
applications, instead of and in support of the conventional diagnostic
imaging technologies. NanoParticles are “dull” and consequently visible
to conventional In Vivo Diagnostic technologies (NMR, PET,…). Moreover,
thanks to their interesting features, increased image resolution, absence of
cytotoxicity and, in particular, their high diffusion capacity and their variable
controlled size, they can enhance permeability and retention at cancer cells
level.
According to specific customer needs, we can design and produce fluorescent or
magnetic NanoParticles to be used as contrast agents and/or tracers.
ACZON CUSTOM MADE
CUSTOM MADE FOR PHARMA
APPLICATIONS: NanoCarriersTM
The use of nanotechnology in medicine and, more specifically drug delivery,
is set to spread rapidly. Currently many substances are being investigated for
drug delivery and more specifically for cancer therapy.
Interestingly, pharmaceutical sciences are using nanoparticles to reduce
toxicity and side effects of drugs. The reason why these nanoparticles are
attractive for medical purposes is due to their important and unique features,
such as their surface to mass ratio, which is much larger than that of other
particles, their quantum properties and their ability to adsorb and carry other
compounds. NanoParticles consist of at least two components, one of which is
a pharmaceutically active ingredient. The primary goals for research of nanobio-technologies in drug delivery include:
·
·
·
·
more specific drug targeting and delivery,
reduction in toxicity while maintaining therapeutic effects,
greater safety and biocompatibility,
faster development of new safe medicine (C.1), and extended circulation
half-life and improved therapeutic index (C.2).
References C - Custom made for pharma
applications:
1- De Jong W.H. et al., “Drug delivery
and nanoparticles: Applications and
hazards”, Int. J. of Nanomedicine,
2008.
2- Petros R.A. et al., “Strategies in the
design of nanoparticles for therapeutic
applications”, Nature Reviews Drug
Discovery, 2010.
3- Luo J. et al, “Size-Tunable,
Multifunctional Micelles for Efficient
Paclitaxel Delivery for Cancer
Treatment”, Bioconugate. Chem.,
2010.
4- Abhimanyu S. et al., “Harnessing
structure-activity
relationship
to
engineer a cisplatin nanoparticle for
enhanced antitumor efficacy”, PNAS,
2010.
5- Tennant D.A. et al., “Targeting
metabolic transformation for cancer
therapy”, Nature Reviews, 2010.
The figure below highlights the various surface modifications that are commonly
pre-engineered, such as cellular targeting, particle ‘stealthing’ and organelle
targeting. Ligands to extend circulation half-life and to reduce immunogenicity
(usually polyethylene glycol (PEG) chains) are linked to the surface of the
nanoparticle together with ligands to promote targeting.
These ligands can be antibodies, aptamers or small molecules known to
bind to surface proteins expressed on target cells or that are capable of
guiding particle localization once inside the cell. Chemotherapeutics or other
biologically relevant cargo are encapsulated inside the nanoparticle.
Release of the cargo at the intended site of action is typically achieved through
the incorporation of a stimuli-responsive material that changes state upon
exposure to the targeted environment (C.2).
Fig. Schematic
representation of an
engineered nanoparticle
(Petros R.A. et al.,
“Strategies in the design
of nanoparticles for
therapeutic applications”,
Nature Reviews Drug
Discovery, 2010).
Why Aczon NanoParticles for Pharma applications?
Aczon NanoParticles, synthesized with specific biomolecules, are very
attractive for drug delivery applications, because they are innovative tools
that offer distinctive features and advantages (high diffusion capacity, easier
to reach the target cells, considerable concentration of the active principle,
effective concentration in vivo and increase local drug concentration).
We can incorporate drugs or other cytotoxic molecules and/or synthesize NPs with
specific bio-molecules that are of great interest to researchers and manufacturers.
ACZON CUSTOM MADE
CUSTOM MADE FOR ENVIRONMENTAL
APPLICATIONS
Sensing of biological agents, diseases, and toxic materials is an important
goal for biomedical diagnosis, forensic analysis, and environmental
monitoring. The unique physicochemical properties of NPs coupled with
the inherent increase in signal-to-noise ratio provided by miniaturization
makes these systems promising candidates for sensing applications. The
integration of nanoparticles with biomolecules in the area of biosensing has
implemented different subset of environmental applications: colorimetric
sensing, fluorescence sensing, chemical and electrochemical sensing.
As example of colorimetric sensing, gold nanoparticles exhibit unique optical
and electronic properties based on size and shape. They show an intense
absorption peak from 500 to 550 nm arising from surface plasmon resonance
(SPR). The SPR band is sensitive to the surrounding environment, signaling
changes in solvent and binding: a particularly useful output is the red-shift (to
ca. 650 nm). This phenomenon leads to the popular and widely applicable
colorimetric sensing (D.5).
The detection and monitoring of microoganisms can be further accelerated
using nanoparticles in a fluorescence labeling system, such as microfluidic
devices, nanoparticle-based fluorescence reporting systems and others
(D.3). Antibodies against antigens, specific for E. coli strain O157, were
conjugated with fluorescent silica nanoparticles and used in immunological
assay to achieve rapid bacterial detection at the single-cell level (as shown in
the figure below). With the improvement in the fluorescence reporting system,
the fluorescence intensity emitted by one E. coli O157 cell was sufficient to be
detected using a normal spectrofluorometer or to be accurately enumerated
using a flow cytometer (D.2, D.4).
Several studies of chemical sensing have utilized bimetallic nanoparticles as
an effective oxidant in the cleanup of environmental contaminants, mainly
because nanoparticles can diffuse or penetrate into a contamination zone
that microparticles are unable to reach (D.4).
References D - Custom made for
environmental applications:
1- Zhao, X. J. et al., “A rapid bioassay
for single bacterial cell quantitation
using bioconjugated nanoparticles”.
Proc. Nat. Acad. Sci., 2004.
2- Tan W. et al, “Bionanotechnology
Based
on
SilicaNanoparticles”,
Medicinal Research Reviews, 2004.
3- Zhang, Q. et al, “Microbial detection
in microfluidic devices through dual
staining of quantum dots-labeled
immunoassay and RNA hybridization”,
Anal. Chim. Acta, 2005.
4- Liu W., “Nanoparticles and
their biological and environment
applications”, J. of Biosci. Bioeng.,
2006.
5- De M. et al., “Applications of
Nanoparticles in Biology”, Adv.
Mater., 2008.
Fig. Images of bacterial
cells. (A) SEM image of E.
coli O157:H7 cell incubated
with Ab-NPs. (B) SEM
image of E. coli DH5α cell
(negative control) incubated
with Ab-NPs for E. coli
O157:H7. (C) Fluorescence
image of E. coli O157:H7
after incubation with
Ab-NPs. The fluorescence
intensity is strong, enabling
single-bacterium cell
identification in aqueous
solution (Zhao X. J. et al.,
PNAS, 2004).
Why Aczon NanoParticles for Environmental applications?
Aczon team has outstanding expertise in organic and inorganic synthesis
of molecules and NanoParticles doped and/or functionalized with different
chemical groups and crosslinkers or conjugated with bio-molecules, so
we can synthesize different kinds of NPs: especially Silica NanoParticles
(proprietary technology); alternatively, to better meet the needs of customers,
we can offer and suggest other ones (such as gold and many other).
We can incorporate special molecules of the customer and conjugate or functionalize
NPs according to specific requests.
ACZON CUSTOM MADE
CUSTOM MADE GUIDELINES
1- Type of NanoParticles (Silica, Gold, other).
2- NanoParticles size: Silica (range 5-100nm), Gold (range 15-200nm), other (if
possible).
3- Core: fluorescent molecules (different fluorophores with specific absorbance
and emission), small drugs (Doxorubicin, Cisplatin, other drug molecules or a
mix of them) and other chemical compounds.
4- Shell: functionalization with different chemical groups (such as -NH2, COOH,
maleimide, -N3, -SH and others if possible).
5- Bio-conjugation: conjugation with protein (such as antibodies), peptides,
nucleic acids and other bio or chemical molecules.
6- Special requirements: buffer, concentration, solubility and others.
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7- Testing requirements: standard test, endotoxin test, other test required if
possible.
Special requirements
The guidelines in “tangram system”: a great project for ACZON Custom Made.
ACZON
CUSTOM
MADE:
designed for
customer needs
ACZON CUSTOM MADE
Plan
Deliver
ACZON
CUSTOM
MADE:
designed for
customer needs
Fig. Schematic
representation
of synthesized NPs
incorporating the
customer’s molecules,
and conjugated or
functionalized according
to specific requests.
Develop
Act
PLAN
- Establish customer needs (applications/
conventional technology problems…)
- Prepare a preliminary definition of the product’s
specifications and performances in collaboration
with your scientific consultant
- Prepare a feasibility study and design the project
- Project approval
DEVELOP
- Produce the prototype
- Validate the master plan
- Assess the reagent’s reproducibility,
specificity, stability and ruggedness
- Present the results
- Customer approval/modifications
ACT
- Production scale-up
DELIVER
- Delivery to the customer
FEEDBACK
- Customer’s assessment of the product
- Technical support from Aczon’s Custom Made
Team
Call us or check out our website for more technical information!
ACZON S.r.l.
Via Lavino, 265-D - 40050 - Monte San Pietro - Bologna - ITALY Tel.: +39 0516759711 Fax: +39 0516759799
www.aczonpharma.com
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