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Definition:- A Nanoparticle or ultrafine particle is usually
defined as a particle of matter that is between 1 and 100
nanometers in diameter. The term is sometimes used for
larger particles, up to 500nm, or fibers and tubes that are
less than 100nm in only two directions.
Arguably the oldest and easiest nanoparticles to make are of
carbon: the use of carbon black from fuel-rich partial
combustion for ink, pigment, and tatoos dates back more
than 3000 years.
Nanoparticles
1 Origin:-
Natural
Anthropogenic
2 Size:-
1-10nm
10-100nm
over 100nm
3 Chemical composition:-
Inorganic substance, Organic substance and elements of
living Kingdom
Classification of nanoparticles
These criteria are presented synthetically in figure
 divided porous materials and pore size into three
categories,
 microporous (<2 nm) Example :- Zeollites, Metal
Organic frameworks.
 mesoporous (2–50 nm) Example:- Oxides of
Niobium, titanium, tantalum, zirconium, cerium.
 and macroporous (>50 nm) Example:- Binary Metals
oxide, Organic polymer Gel.
Porous nanomaterial
 First, on the tissue engineering utilized porous
aluminum oxide membranes as cell growth
substrates for osteoblast cells which was a
comparison study among several different porous
and non-porous aluminum oxides.
few advances of porous nanomaterials
 titanium oxide nanotubes can effectively direct the
adhesion and proliferation of mammalian cells on
anodized porous substrates. The critical factor in the case
of mesenchymal stem cells’ adhesion, spreading, growth,
and differentiation was the diameter of the as-prepared
nanotubes which meant that the porosity of the substrate
controlled the bioprocesses involved in stem cell biology
to a noticeable degree.
 TiO2 nanotubes (100 nm diameter with aspect ratio of
approximately 1000) can enhance blood clotting rates
Titanium Oxide
Titanium dioxide (TiO2):-
Titania (TiO2) has received much attention in
materials sciences and engineering due to its
optoelectronic properties. For example, TiO2 has
been utilized as photocatalysts for photochemical
hydrogen production and for self-cleaning
windows. In the cosmetic industry, titania is the
main ingredient in many commercial sunscreens
along side ZnO due to its property of UV
absorption.
(1) Anatase
(2) Rutile
(3) Brookite
These phases are responsible for the photo catalytic
behavior of Titanium Oxide
Phases of Titanium Oxide
 cell toxicology in relation to TiO2 particle size and
crystal phase and have done studies with dermal
fibroblasts and human lung epithelial cells as well as
with rats which suggest that photoactivation of
anatase TiO2 will increase cytotoxicity but
concentrations over 100 mg/mL will be significant
enough to cause any ill effects.
Anatase
 Few excerpts within the past several years.LDH
(lactate dehydrogenase) assay revealed TiO2 to be
the least toxic material from sub-100 nm up to 1 mm.
According to studies toxicology assessed using cell
membrane damage assays, metal oxides are toxic in
the following order:
 TiO2 < Al2O3 < SiO2 regardless of size under 1 μm.
Toxicity of Metal Oxide
 Metal oxide hemostatic agents such as porous
zeolites and bioglass (SiO2–P2O5–CaO) have been
reported much earlier in time by Stucky and co-
workers to effectively enhance the rate of clotting
times both in vitro and in vivo
 The porous metal oxides can play key roles in
controlling the bioprocesses involved in the blood
clotting cascade.
Metal Oxide/Zeolites
 As particle size is decreased to the few tens of
nanometers, ferromagnetic materials will have only a
single magnetic domain, and all magnetic spins
within that domain will be aligned, while thermal
motion of such particles relative to one another will
control the bulk magnetic properties. These
materials are referred to as superparamagnetic and
are excellent MRI (magnetic resonance imaging)
contrast agents
Magnetic Nanomaterials
 Superparamagnetic inorganic oxides (SPIO) such as
Fe3O4 are proving especially useful in tumor
targeting and MRI imaging in biomedical application.
Water-soluble superparamagnetic iron oxide (WSIO)
nanoparticles, for instance, can be additionally
passivated with cancer targeting agents (e.g.
antibodies) and in vivo MRI imaging can be done to
monitor the circulation and specific attachment to
the cancer induced area. Iron oxides have also been
utilized in bioimaging for neuroscienc
Superparamagnetics iron oxide
 modified SPIO nanoparticles that can target cellular
mRNAs and detect active transcriptions of specific
mRNAs in vivo using antisense imaging agents
phosphorothioate oligodeoxynucleotide) coupled
with MRI imaging. This type of research can lead to
the development of real-time MRI detection methods
where CNS disease models linked to mRNA alteration
can be identified.
Modified SPIO nanoparticles
 Ab1–40 peptide modified iron oxide nanoparticles to
detect Ab in transgenic mice in vivo.
 Summary of Nanomagnetic materials:- magnetic
nanomaterials, especially superparamagnetic iron
oxides, can be utilized in three distinctive
neurological applications which include tracking
transplanted cells (e.g. stem cells), identifying
transcription efficiencies, and detecting amyloid beta
peptides in diseased brains.
Modified iron oxide nanoparticles
 the development of potent wound-dressing materials
(blood clotting agents) that are capable of arresting
hemorrhage due to traumatic injury is another
emerging application using materials chemistry to
control bioprocesses and one of the most effective
wounddressing materials currently available is a
nanoporous zeolite called QuikClot (QC).
Zeolites and clays
 the isoelectric points of different inorganic surfaces, as
measured in simulated body fluid (SBF), can be used as primary
determinants to selectively and in a predictable manner
accelerate or inhibit blood coagulation . One example of the
many metal oxides based materials that were investigated was
clays. Chemical and physical properties, including variable
swelling capacities, particle morphologies, surface charge, and
the ability to control the local electrolyte balance through ion
exchange are tunable variables available in clay science. It was
found that surface charge in SBF for clays such as kaolin
correlated very well with the wide range of blood clotting
activities of porcine whole blood or plasma.
Blood clotting and Inhibiting clay
 Hemostasis properties of high-surface-area porous
silica, the has shown that the selective variation of
window/pore sizes at the sub-50 nm range strongly
dictated the rate at which blood clots are formed in
human plasma . This indicates that pore sizes in this
size range directly impact the accessibility and
diffusion of clotting-promoting proteins to and from
the interior surfaces of the porous silica particles.
Surface charged Nanoparticles
 silica (SiO2) has been studied more widely due to an
occupational lung disease called silicosis which is linked
to crystalline phase silica.
 few good examples of SiO2 nanostructured materials with
a focus on recent synthetic particles that have
multifunctionality . SiO2 sub-50 nm silica nanoparticles
incorporating a fluorophore and an MRI agent were
synthesized and cell viability was checked with a one day
colorimetric tetrazolium assay using monocyte cells
which revealed the non-toxic nature of that particular
multifunctional particle
Silicon Dioxide
Mesoporous SiO2:- Mesoporous SiO2 spheres have been
prepared and utilized in several biological applications in
the past few years including drug delivery studies . In a
recent anti-cancer drug delivery study done by UCLA ,
approximately 130 nm amine group functionalized
mesoporous SiO2 spheres were formed and surface
modified with alkyl phosphate groups. Cytotoxicity tests
on several different cancer cell lines (e.g. PANC-1, AsPC-
1) revealed practically no toxicity unless the anti-cancer
drug was loaded and subsequently released over time. In
another protein, polymer functionalized SiO2,
luminescent nanobeads of approximately 20 nm were
tested for its cytotoxicity (< 6 h) via apoptosis and
necrosis assays .
 Iron in the presence of an oxidant (e.g. air) will become
iron oxide (i.e. rust). There are several phases of iron
oxides which include Haematite (a-Fe2O3), Magnetite
(Fe3O4), Maghemite (g Fe2O3), b-Fe2O3, e-Fe2O3, Wu¨
stite (FeO).
 Among them, magnetite (Fe3O4) nanoparticles have been
the subject of research for many years in hopes of using
them for biomedical research.
 Sub-10 nm Fe3O4 nanoparticles have been particularly
useful as a superparamagnetic MRI probe that can be
made to target-specific cells and tissues inside the body
Iron Oxide
 iron oxide nanoparticles affected PC12 cells’ ability to
differentiate in response to nerve growth factors
(NGF) in a concentration dependent manner.
 For instance, Western blotting revealed that growth
associated protein GAP-43 level decreased
dramatically when the NGF concentration went from
0.15 to 1.5 mM then 15 mM which alerted.
Toxicity of Iron Oxide
 50 nm iron oxide nanopaticles as tumor homing vehicles that
has been conjugated to a tumor targeting peptide CREKA (Cys-
Arg-Glu-Lys-Ala). CREKA allows the nanoparticle to recognize
clotted plasma proteins and bind to vessel walls and tumor
stroma. Interestingly, these nanoparticles accumulate in tumor
vessels; induce blood clotting which increases binding sites for
additional particles to home in to. This type of controlled and
targeted toxicity is a new state-of-the-art use of iron oxide
nanoparticles in comparison to their sole use as image contrast
agents. It will be beneficial for the neuroscience community to
bench mark such efforts from the cancer research community
and follow the biological target based approaches and
implement them to known targets in neurological disorders.
Iron Oxide and Cancer
 Among carbon-based materials, carbon nanotubes have been well
utilized in recent biological applications. Excellent review papers
already exist for CNTssowe will focus on new types of spherical and
non-tubular forms of carbon that was developed for biological
applications . The first example is carbon nanohorns by Iijima and co-
workers. Processed in a similar fashion as CNT’s, researchers were
able to synthesize high surface area carbon materials that have tube-
like carbon sticking outward but in a spherical overall shape and are
approximately 100 nm in size. Cytotoxic assays show practically no
toxicity. The second one is carbon nanodots (sub-10 nm) which were
strongly two-photon active and emit in the visible range . In vitro tests
suggest that the carbon nanodots can be internalized into mammalian
cells and fluorescent microscopy imaging was possible. A third recent
class is (fluorescent) diamond nanoparticles which were found to be
noncytotoxic and were used as single-particle biomarkers on
mammalian cells.
Carbon Nanoparticles
Some carbon nanoparticles
 Patterned surfaces, particularly, created with PDMS
(poly (dimethylsiloxane)) elastomer have been of
high interest to many for cell attachment studies both
for eukaryotic and prokaryotic.
 lab-on-chip systems (made out of PDMS and slide
glass) which allow neuronal cell bodies to be
spatially separated from the out-growing neurites
and axons.
Nanowires and patterned surfaces
 nanoparticles engineered for biomedical applications
involve nanoparticles having multiple components in the
nanomaterial . In most cases, as depicted in the schematic,
a multifunctional nanoparticle system (MFNPS) would be
comprised of four main components: a matrix which is
few hundred nanometers in size or smaller, a magnetic
domain (e.g. Fe3O4) for MR imaging, an optical probe
(usually fluorescent such as FITC) for microscopy, and
pores or functionality that allows the incorporation of a
small molecule (i.e. therapeutic agent) or a biomolecule
(i.e. antibody).
Multifunctional nanoparticle
 Type 1:- is non-porous but spherical SiO2 based sub-
100 nm nanoparticles with two or more components
Multifunctional nanoparticle systems
Type 2:- is sub-200 nm spherical nanoparticles that is either porous or can
incorporate
and, in time, release small molecules such as drug molecules.
Type 3:- is sub-20 nm nanoparticles with functionalizable ligands or biomolecules
stabilized (passivated) onto the nanoparticles and are, in most cases, first synthesized
in organic conditions and then phase exchanged.
Type 4:- is non-spherical nanoparticle systems that have multiple
components such as fluorescent tags and antibodies. This last
type 4 MFNPs will essentially have very different biological
responses compared to spherical systems. According to a recent
study by Discher and co-workers showed that particle flow and
subsequent delivery of drugs are affected by shape in vivo.
Filament (non-spherical) type particles resided approximately
ten times longer than spherical particles and due to their
prolonged existence drug delivery was more effective as well. Cell
uptake efficiencies also differed.
Thank You

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Nanoparticles definitions their classification and biomedical approach to nanotechnology

  • 1. Definition:- A Nanoparticle or ultrafine particle is usually defined as a particle of matter that is between 1 and 100 nanometers in diameter. The term is sometimes used for larger particles, up to 500nm, or fibers and tubes that are less than 100nm in only two directions. Arguably the oldest and easiest nanoparticles to make are of carbon: the use of carbon black from fuel-rich partial combustion for ink, pigment, and tatoos dates back more than 3000 years. Nanoparticles
  • 2. 1 Origin:- Natural Anthropogenic 2 Size:- 1-10nm 10-100nm over 100nm 3 Chemical composition:- Inorganic substance, Organic substance and elements of living Kingdom Classification of nanoparticles
  • 3. These criteria are presented synthetically in figure
  • 4.  divided porous materials and pore size into three categories,  microporous (<2 nm) Example :- Zeollites, Metal Organic frameworks.  mesoporous (2–50 nm) Example:- Oxides of Niobium, titanium, tantalum, zirconium, cerium.  and macroporous (>50 nm) Example:- Binary Metals oxide, Organic polymer Gel. Porous nanomaterial
  • 5.  First, on the tissue engineering utilized porous aluminum oxide membranes as cell growth substrates for osteoblast cells which was a comparison study among several different porous and non-porous aluminum oxides. few advances of porous nanomaterials
  • 6.  titanium oxide nanotubes can effectively direct the adhesion and proliferation of mammalian cells on anodized porous substrates. The critical factor in the case of mesenchymal stem cells’ adhesion, spreading, growth, and differentiation was the diameter of the as-prepared nanotubes which meant that the porosity of the substrate controlled the bioprocesses involved in stem cell biology to a noticeable degree.  TiO2 nanotubes (100 nm diameter with aspect ratio of approximately 1000) can enhance blood clotting rates Titanium Oxide
  • 7. Titanium dioxide (TiO2):- Titania (TiO2) has received much attention in materials sciences and engineering due to its optoelectronic properties. For example, TiO2 has been utilized as photocatalysts for photochemical hydrogen production and for self-cleaning windows. In the cosmetic industry, titania is the main ingredient in many commercial sunscreens along side ZnO due to its property of UV absorption.
  • 8. (1) Anatase (2) Rutile (3) Brookite These phases are responsible for the photo catalytic behavior of Titanium Oxide Phases of Titanium Oxide
  • 9.  cell toxicology in relation to TiO2 particle size and crystal phase and have done studies with dermal fibroblasts and human lung epithelial cells as well as with rats which suggest that photoactivation of anatase TiO2 will increase cytotoxicity but concentrations over 100 mg/mL will be significant enough to cause any ill effects. Anatase
  • 10.  Few excerpts within the past several years.LDH (lactate dehydrogenase) assay revealed TiO2 to be the least toxic material from sub-100 nm up to 1 mm. According to studies toxicology assessed using cell membrane damage assays, metal oxides are toxic in the following order:  TiO2 < Al2O3 < SiO2 regardless of size under 1 μm. Toxicity of Metal Oxide
  • 11.  Metal oxide hemostatic agents such as porous zeolites and bioglass (SiO2–P2O5–CaO) have been reported much earlier in time by Stucky and co- workers to effectively enhance the rate of clotting times both in vitro and in vivo  The porous metal oxides can play key roles in controlling the bioprocesses involved in the blood clotting cascade. Metal Oxide/Zeolites
  • 12.  As particle size is decreased to the few tens of nanometers, ferromagnetic materials will have only a single magnetic domain, and all magnetic spins within that domain will be aligned, while thermal motion of such particles relative to one another will control the bulk magnetic properties. These materials are referred to as superparamagnetic and are excellent MRI (magnetic resonance imaging) contrast agents Magnetic Nanomaterials
  • 13.  Superparamagnetic inorganic oxides (SPIO) such as Fe3O4 are proving especially useful in tumor targeting and MRI imaging in biomedical application. Water-soluble superparamagnetic iron oxide (WSIO) nanoparticles, for instance, can be additionally passivated with cancer targeting agents (e.g. antibodies) and in vivo MRI imaging can be done to monitor the circulation and specific attachment to the cancer induced area. Iron oxides have also been utilized in bioimaging for neuroscienc Superparamagnetics iron oxide
  • 14.  modified SPIO nanoparticles that can target cellular mRNAs and detect active transcriptions of specific mRNAs in vivo using antisense imaging agents phosphorothioate oligodeoxynucleotide) coupled with MRI imaging. This type of research can lead to the development of real-time MRI detection methods where CNS disease models linked to mRNA alteration can be identified. Modified SPIO nanoparticles
  • 15.  Ab1–40 peptide modified iron oxide nanoparticles to detect Ab in transgenic mice in vivo.  Summary of Nanomagnetic materials:- magnetic nanomaterials, especially superparamagnetic iron oxides, can be utilized in three distinctive neurological applications which include tracking transplanted cells (e.g. stem cells), identifying transcription efficiencies, and detecting amyloid beta peptides in diseased brains. Modified iron oxide nanoparticles
  • 16.  the development of potent wound-dressing materials (blood clotting agents) that are capable of arresting hemorrhage due to traumatic injury is another emerging application using materials chemistry to control bioprocesses and one of the most effective wounddressing materials currently available is a nanoporous zeolite called QuikClot (QC). Zeolites and clays
  • 17.  the isoelectric points of different inorganic surfaces, as measured in simulated body fluid (SBF), can be used as primary determinants to selectively and in a predictable manner accelerate or inhibit blood coagulation . One example of the many metal oxides based materials that were investigated was clays. Chemical and physical properties, including variable swelling capacities, particle morphologies, surface charge, and the ability to control the local electrolyte balance through ion exchange are tunable variables available in clay science. It was found that surface charge in SBF for clays such as kaolin correlated very well with the wide range of blood clotting activities of porcine whole blood or plasma. Blood clotting and Inhibiting clay
  • 18.  Hemostasis properties of high-surface-area porous silica, the has shown that the selective variation of window/pore sizes at the sub-50 nm range strongly dictated the rate at which blood clots are formed in human plasma . This indicates that pore sizes in this size range directly impact the accessibility and diffusion of clotting-promoting proteins to and from the interior surfaces of the porous silica particles. Surface charged Nanoparticles
  • 19.  silica (SiO2) has been studied more widely due to an occupational lung disease called silicosis which is linked to crystalline phase silica.  few good examples of SiO2 nanostructured materials with a focus on recent synthetic particles that have multifunctionality . SiO2 sub-50 nm silica nanoparticles incorporating a fluorophore and an MRI agent were synthesized and cell viability was checked with a one day colorimetric tetrazolium assay using monocyte cells which revealed the non-toxic nature of that particular multifunctional particle Silicon Dioxide
  • 20. Mesoporous SiO2:- Mesoporous SiO2 spheres have been prepared and utilized in several biological applications in the past few years including drug delivery studies . In a recent anti-cancer drug delivery study done by UCLA , approximately 130 nm amine group functionalized mesoporous SiO2 spheres were formed and surface modified with alkyl phosphate groups. Cytotoxicity tests on several different cancer cell lines (e.g. PANC-1, AsPC- 1) revealed practically no toxicity unless the anti-cancer drug was loaded and subsequently released over time. In another protein, polymer functionalized SiO2, luminescent nanobeads of approximately 20 nm were tested for its cytotoxicity (< 6 h) via apoptosis and necrosis assays .
  • 21.  Iron in the presence of an oxidant (e.g. air) will become iron oxide (i.e. rust). There are several phases of iron oxides which include Haematite (a-Fe2O3), Magnetite (Fe3O4), Maghemite (g Fe2O3), b-Fe2O3, e-Fe2O3, Wu¨ stite (FeO).  Among them, magnetite (Fe3O4) nanoparticles have been the subject of research for many years in hopes of using them for biomedical research.  Sub-10 nm Fe3O4 nanoparticles have been particularly useful as a superparamagnetic MRI probe that can be made to target-specific cells and tissues inside the body Iron Oxide
  • 22.  iron oxide nanoparticles affected PC12 cells’ ability to differentiate in response to nerve growth factors (NGF) in a concentration dependent manner.  For instance, Western blotting revealed that growth associated protein GAP-43 level decreased dramatically when the NGF concentration went from 0.15 to 1.5 mM then 15 mM which alerted. Toxicity of Iron Oxide
  • 23.  50 nm iron oxide nanopaticles as tumor homing vehicles that has been conjugated to a tumor targeting peptide CREKA (Cys- Arg-Glu-Lys-Ala). CREKA allows the nanoparticle to recognize clotted plasma proteins and bind to vessel walls and tumor stroma. Interestingly, these nanoparticles accumulate in tumor vessels; induce blood clotting which increases binding sites for additional particles to home in to. This type of controlled and targeted toxicity is a new state-of-the-art use of iron oxide nanoparticles in comparison to their sole use as image contrast agents. It will be beneficial for the neuroscience community to bench mark such efforts from the cancer research community and follow the biological target based approaches and implement them to known targets in neurological disorders. Iron Oxide and Cancer
  • 24.  Among carbon-based materials, carbon nanotubes have been well utilized in recent biological applications. Excellent review papers already exist for CNTssowe will focus on new types of spherical and non-tubular forms of carbon that was developed for biological applications . The first example is carbon nanohorns by Iijima and co- workers. Processed in a similar fashion as CNT’s, researchers were able to synthesize high surface area carbon materials that have tube- like carbon sticking outward but in a spherical overall shape and are approximately 100 nm in size. Cytotoxic assays show practically no toxicity. The second one is carbon nanodots (sub-10 nm) which were strongly two-photon active and emit in the visible range . In vitro tests suggest that the carbon nanodots can be internalized into mammalian cells and fluorescent microscopy imaging was possible. A third recent class is (fluorescent) diamond nanoparticles which were found to be noncytotoxic and were used as single-particle biomarkers on mammalian cells. Carbon Nanoparticles
  • 26.  Patterned surfaces, particularly, created with PDMS (poly (dimethylsiloxane)) elastomer have been of high interest to many for cell attachment studies both for eukaryotic and prokaryotic.  lab-on-chip systems (made out of PDMS and slide glass) which allow neuronal cell bodies to be spatially separated from the out-growing neurites and axons. Nanowires and patterned surfaces
  • 27.  nanoparticles engineered for biomedical applications involve nanoparticles having multiple components in the nanomaterial . In most cases, as depicted in the schematic, a multifunctional nanoparticle system (MFNPS) would be comprised of four main components: a matrix which is few hundred nanometers in size or smaller, a magnetic domain (e.g. Fe3O4) for MR imaging, an optical probe (usually fluorescent such as FITC) for microscopy, and pores or functionality that allows the incorporation of a small molecule (i.e. therapeutic agent) or a biomolecule (i.e. antibody). Multifunctional nanoparticle
  • 28.  Type 1:- is non-porous but spherical SiO2 based sub- 100 nm nanoparticles with two or more components Multifunctional nanoparticle systems
  • 29. Type 2:- is sub-200 nm spherical nanoparticles that is either porous or can incorporate and, in time, release small molecules such as drug molecules. Type 3:- is sub-20 nm nanoparticles with functionalizable ligands or biomolecules stabilized (passivated) onto the nanoparticles and are, in most cases, first synthesized in organic conditions and then phase exchanged.
  • 30. Type 4:- is non-spherical nanoparticle systems that have multiple components such as fluorescent tags and antibodies. This last type 4 MFNPs will essentially have very different biological responses compared to spherical systems. According to a recent study by Discher and co-workers showed that particle flow and subsequent delivery of drugs are affected by shape in vivo. Filament (non-spherical) type particles resided approximately ten times longer than spherical particles and due to their prolonged existence drug delivery was more effective as well. Cell uptake efficiencies also differed.