This document discusses the biomedical applications of nanoparticles. It begins by defining nanoparticles as particles between 1-100 nanometers in size. It then outlines several types of nanoparticles that have biomedical applications, including gold nanoparticles, quantum dots, iron oxide nanoparticles, carbon nanotubes, dendrimers, and lipid-based nanoparticles. For each type of nanoparticle, it provides examples of their biomedical uses such as drug delivery, cancer treatment, biomedical imaging, and diagnosis. It also discusses considerations for the toxicity of nanoparticles and their potential effects on cells and animals. In closing, it covers antimicrobial nanoparticles and their use against bacteria, fungi, and viruses.
2. NANOPARTICLES
Nanoparticles are particles between 1 and 100
nanometers in size.
In nanotechnology , a particle is defined as a small
object that behaves as a whole unit with respect to
its transport and properties.
Nanomaterials hold immense promise for
significantly improving existing diagnosis , therapy
and designing novel approaches to treat a variety
of human ailments.
3. NANOPARTICLES While some of the applications of nanotechnology
have been translated into clinical settings, many
more potential uses of nanomedicines have been
demonstrated in experimental systems.
Since a variety of materials can be nanosized, the
scope of nanomedicine is also large and may even
become larger.
At the same time, the impact of nanomaterials on
cellular and animal models will need to be carefully
evaluated under both acute and chronic exposures
at toxicological and pharmacological doses.
5. GOLD
Inorganic nanoparticles are emerging as versatile
tools in imaging as a result of their unique
chemical, physical and optical properties .
Gold nanoparticles were discovered > 100 years ago
and owing to their surface chemistry, projected
biocompatibility, relatively low short-term toxicity,
high atomic number and high X-ray absorption
coefficient.
Gold nanoparticles have received significant
interest recently for use in multiple imaging
technologies.
6. APPICATIONS OF GOLD
NANOPARTICLES
Gold nanoparticles may be used in different domains,
one of most important being the biomedical field.
They have suitable properties for :
controlled drug delivery
cancer treatment
biomedical imaging
diagnosis and many others due to their excellent
compatibility with the humans, low toxicity and
tunable stability, small dimensions, and possibility to
interact with a variety of substances.
7. APPICATIONS OF GOLD
NANOPARTICLES
Gold nanoparticles are intensively studied in
biomedicine, and recent studies revealed the fact
that they can cross the blood-brain barrier, may
interact with the DNA and produce genotoxic
effects.
Because of their ability of producing heat, they can
target and kill the tumors, being used very often in
photodynamic therapy.
Gold nanoparticles have also emerged in
diagnostics as colorimetric biosensors
8. Quantum dots
Quantum dots (QDs) are fluorescent semiconductor
nanocrystals (∼ 1 – 100 nm) with unique optical and
electrical properties .
Quantum dots are increasingly used as fluorophores
for in vivo fluorescence imaging.
Fluorescence imaging has several advantages compared
with other imaging modalities because this method has
good sensitivity and is non-invasive in nature, using
readily available and relatively inexpensive instruments.
Being an optical technique, it is limited in terms of
tissue penetration depth. A wide variety of in vivo studies
have validated the potency of QDs.
9. Iron oxide nanoparticles
Magnetic nanoparticles have received considerable
attention because of their potential use in optical,
magnetic and electronic devices.
Magnetic iron oxide nanoparticles have been
functionalized with antibodies, nucleosides, proteins and
enzymes for directing them to diseased tissues such as
tumors.
MRI is a non-invasive medical imaging technique that is
commonly used in clinical medicine to visualize the
structure and function of tissues.
MRI is based on the behavior, alignment and interaction
of protons in the presence of an applied magnetic field.
10. Carbon nanotubes
CNT’s are used as field emission devices, tips for
scanning microscopy, nanoscale transistors, or
components for composite materials.
A few bioimaging applications using CNTs have
been developed for cancer cell destruction,
detection and dynamic imaging.
SWNTs(single walled carbon nanotubes)
covalently linked to visible-wavelength
fluorophores have been imaged in cells using
confocal microscopy .
11. Dendrimers
Dendrimers are well-defined, highly branched
molecules that are synthesized with precise structural
control and low polydispersity .
Magnevist, a gadolinium(III)-
diethylenetriaminepentaacetic acid (Gd-DTPA)
complex, is a commonly used contrast agent for MRI.
12. Polyelectrolyte complex
nanoparticles
Polyelectrolyte complex nanoparticles have attractive
properties for imaging and drug delivery.
PECs have been established as potential materials for
gene delivery because of their relatively efficient
transfection efficiency and simple formulation .
More recently, these nanocarriers have proved
effective for entrapping and delivering small
molecules, peptides, RNAs and even large proteins .
Few reports are also available on their use in
biomedical imaging applications and also as
therapeutic agents.
13. Calcium phosphate nanoparticles
Calcium phosphate nanoparticles have received
attention because of reports of low toxicity,
biocompatibility and solubility in cells.
Calcium phosphate has been used as a delivery
vehicle for DNA and has been studied as a
nanoparticle for gene delivery.
Also, these particles have been used for the
encapsulation of organic molecules, fluorescent
dyes and chemotherapeutic drugs, suggesting the
potential for in vivo biomedical imaging and drug
delivery applications.
14. Perfluorocarbon nanoparticles
Perfluorocarbon nanoparticles (PFCNPs) have
received considerable attention for their applications
in molecular imaging and targeted drug delivery
applications.
PFCNPs act as a platform to carry contrast-enhancing
agents or chemotherapeutic drugs.
Functionalized PFCNPs are compatible with several
molecular imaging modalities, including MRI and CT.
Functionalized PFCNP contrast agents have been used
as molecular imaging agents in MRI assessments of
tumor angiogenesis, cellular tracking and
atherosclerosis .
15. Lipid-based nanoparticles
Lipid-based nanoparticles such as liposomes and micelles
have been developed for pharmaceuticals and aim to
address the traditional boundaries to drug delivery .
Mulder et al. pioneered the use of lipid-based
nanoparticles for contrast-enhanced MRI and molecular
imaging applications .
Koole et al. recently developed paramagnetic lipid-coated
silica nanoparticles containing a quantum dot core as a
contrast agent for multimodal imaging (fluorescence and
MRI) of αvβ3-integrin expression on cultured endothelial
cells.
16. Lipid-based nanoparticles
Also, Cressman et al. recently developed an RGD-
labeled lipid incorporated into liposomal
nanoparticles and studied trafficking in cultured
endothelial cells.
Senarath-Yapa et al. furthered this work by
reporting the use of poly(lipid)-coated,
fluorophore-doped silica nanoparticles for
biolabeling and cellular imaging applications .
17.
18.
19. Toxicity considerations
Owing to the rapid growth of nanoparticle use in biomedical
research, the toxicity of these materials should be considered
in detail .
Complete characterization of size , shape, charge , surface
chemistry and material properties is important when
correlating toxicity.
Nanomaterials may agglomerate in vitro or in vivo and may
chemically degrade, making it difficult to relate systematically
nanoparticle toxicity to such a diverse set of materials.
Detailed studies of biodistribution, pharmacokinetics and
local and systemic toxicity for each type of nanoparticle, will
be important in overall toxicity evaluations.
20. ANTIMICROBIAL NANOPARTICLES
Despite numerous existing potent antibiotics and
other antimicrobial means, bacterial infections are
still a major cause of morbidity and mortality.
Moreover, the need to develop additional
bactericidal means has significantly increased due
to the growing concern regarding multidrug-
resistant bacterial strains and biofilm associated
infections.
Consequently, attention has been especially
devoted to new and emerging nanoparticle-based
materials in the field of antimicrobial
chemotherapy.
21. ANTIMICROBIAL NANOPARTICLES
Metals and metal oxides have been widely studied
for their antimicrobial activities.
Metal oxide nanoparticles, well known for their
highly potent antibacterial effect, include silver
(Ag), iron oxide (Fe3O4), titanium oxide (TiO2),
copper oxide (CuO), and zinc oxide (ZnO).
Most metal oxide nanoparticles exhibit
bactericidal properties through reactive oxygen
species (ROS) generation although some are
effective due to their physical structure and metal
ion release.
22. Silver
Of the metal nanoparticles, silver nanoparticles have
been widely used as an effective antimicrobial agent
against bacteria, fungi, and viruses .
Ag and its compounds have long been used for the
disinfection of medical devices and water purification.
In medicine, Ag compounds are commonly applied to
treat burns, wounds, and a variety of infectious
diseases .
Although the Ag nanoparticle mechanism of action is
still not clear, small diameter Ag nanoparticles have a
superior antimicrobial effect to those of a larger
diameter .
23. Titanium Oxide
Titanium dioxide (TiO2) is another metal oxide
that has been extensively studied for its
antimicrobial activities .
TiO2 has long been known for its ability to kill
both Gram-positive and Gram-negative bacteria .
More recent reports have shown its efficiency
against various viral species and parasites.
24. Titanium Oxide
Titanium dioxide (TiO2) NM as antibacterial compounds
have been on the market for quite some time .
They are photocatalytic, their toxicity induced by visible
light, near-UV or UV , stimulates ROS burst.
The ROS damage the membrane, DNA, and many other
macromolecules and functions of the bacterial cell .
TiO2 is effective against many bacteria including spores
of Bacillus , which is the most resistant organism known.
As with other NM, combinations of Ti or TiO2 with
other NM such as Ag were found to have a synergistic
effect and to enhance their activity.
25. Zinc Oxide
Additional broad spectrum bactericidal NM are
ZnO-based nanoparticles .
ZnO nanoparticles were shown to have a wide
range of antimicrobial activity against various
microorganisms, which is significantly dependent
on the chosen concentration and particle size
26. Zinc Oxide
ZnO nanoparticles were shown to inhibit the
growth of methicillin-sensitive S. aureus (MSSA),
methicillin-resistant S. aureus (MRSA), and
methicillin-resistant S. epidermidis (MRSE) strains
and proved to be effective bactericidal agents that
were not affected by the drug-resistant
mechanisms of MRSA and MRSE .
27. Zinc Oxide
Zinc oxide (ZnO) NM are of relatively low cost and
effective in size dependency against a wide range
of bacteria .
These include pathogens such as Klebsiella
pneumonia , Listeria monocytogenes, Salmonella
enteritidis , Streptococcus mutans,
Lactobacillus and E. coli with low toxicity to
human cells.
28. Zinc Oxide
Their white color, UV-blocking, and ability to prevent
biofilm formation makes them suitable for fabric and
glass industries as coating materials designated for
medical and other devices.
Furthermore, treatment using zinc was approved by
the FDA and nowadays Zn is available as a food
additive .
ZnO NM affect bacterial cells by binding to
membranes, disrupting their potential and integrity,
and by inducting ROS production .
In addition and as a result, Zn NM are also weak
mutagens.
29. Iron Oxide and Gold
Fe3O4 nanoparticles and gold (Au) represent an
additional class of antimicrobial materials that are
being researched for their use in health care .
Microbiological assays have proved that surfaces
modified using Fe3O4 nanoparticles demonstrate
antiadherent properties and significantly reduce
both Gram-negative and Gram-positive bacterial
colonization .
Au nanoparticles and nanorods have been
reported to be bactericidal when photothermally
functionalized.
30. Magnesium Oxide
Nano-magnesium oxides (MgO) are additional
antibacterial metal oxide NM that have been shown to
exhibit bactericidal activity.
Nano-MgO particles were reported to exhibit efficient
antimicrobial activity against bacteria (both Gram-
positive and Gram-negative), spores, and viruses.
Magnesium (Mg) can be used in various NM in the
form of MgO or MgX2 (e.g., MgF2) .
In addition to inducing ROS, Mg-containing NM may
directly inhibit essential enzymes of the bacteria .
MgF2 NM were found to prevent biofilm formation
of E. coli and S. aureus .
31. Superparamagnetic Iron Oxide
Superparamagnetic iron oxide (SPION) represents
a relatively new approach using magnetic particles
that cause local hyperthermia in the presence of a
magnetic field or alternatively, they can be coated
by other NM such as Ag and Au and their
magnetic effect can be utilized to penetrate and
destroy biofilms.
32. Nitric Oxide
Nitric oxide (NO) NM differ from other metal NM
by specifically affecting reactive nitrogen species
(RNS), rather than ROS.
NO NM were found to effectively kill methicillin-
resistant S. aureus (MRSA) in skin infections and
to enhance wound healing of normal and diabetic
mice.
NO NM are also effective in biofilm eradication of
multiple bacterial species.
33. Aluminum Oxide
It is not clear if aluminum oxide (Al2O3) nanoparticles are
suitable for antibacterial treatment.
First, their bactericidal effect is relatively mild and they work
only at high concentrations unless in combination with other
NM such as Ag.
Second and more disturbing is their ability to promote
horizontal transfer of multiresistance genes mediated by
plasmids across genera.
The mechanism of action of aluminum NM, as recently
shown for E. coli, is by diffusion and accumulation inside the
cells, causing pit formation, perforation, and membrane
disorganization, leading to cell death .