• Azmi Bin Hassan
• Mohd Nazih Bin Jaafar
• Mohd Farid Bin Saiman
• Mohd ‘Azzim Bin Nordin
• Mohd Faiz Bin Mohd Fuad
• Mohd Fikri Bin Omar
• Mohd Azamudin Bin Abdul Aziz
– Nanotechnology is the understanding and control of
matter at dimensions of roughly 1 to 100 nanometers
– Nanotechnology involves imaging, measuring, modeling,
and manipulating matter in this scale
• Nanotechnology may be able to create many new materials
and devices with a vast range of applications, such as
in medicine, electronics, biomaterials and energy production.
• Humans are exposed to airborne nanomaterials in daily life,
such as nanoparticles found in smoke, drugs, paints,
cosmetics, soaps, shampoos, detergents, sunscreens, tennis
rackets, video screens, coatings, catalysts, concrete.
1. Respiratory System 2. Skin
UPTAKE BY HUMAN
Exposure through respiratory system
Inhalation of nanoparticles leads to deposition of
nanoparticles in respiratory tract and lungs.
Caused lung-related disease. E.g. asthma, bronchitis, lung
cancer, pneumonia etc.
Translocation of nanomaterials therefore could lead to brain.
Exposure through skin
o Nanoparticles may penetrate into sweat glands and hair
o Skin exposure to cosmetics, sunscreens and dusts resulted in
accumulation of nanoparticles.
o Baroli et al. reported that metallic nanoparticles smaller than
10nm could penetrate the hair follicle and stratum corneum
and sometimes reach the viable epidermis.
o However, metallic nanoparticles unable to permeate the skin.
Exposure through Ingestion
Exposure of nanomaterials into gastrointestinal tract can
occur after uptake of daily food, drinks and medicines.
Nanoparticles absorbed by any means can cause cytotoxicity
Cytotoxicity means that nanoparticles prevent cell division,
hinder cell proliferation, damage DNA and biological system
and lead to cell death by biological process called apoptosis.
Apoptosis is a process of deliberate cell self-destruction in an
A size dependent study of copper on mice was carried by chen
etc al. It show that toxicity increase as the size of copper
Quantum dots offer surface manipulation and also show
potential benefit for biomedical research.
Nanoscale contrast agents show potential applications in
magnetic resonance (MR) molecular imaging for clinical
Nanoparticles of cadmium telluride (CdTe) exhibit strong
fluorescence that could be used in solid state lighting and
Carbon nanotubes used for drug delivery to specific target
such as tumor cells. Nanotubes filled with magnetic
nanoparticles help in transporting medicine to target.
The biocompatibility of such nanomaterials remains
questionable due to their adverse effect on human health.
• A wide variety of nanomaterials, such as a very wide variety of
man-made nanostructured materials such as
a. Metallic nanoparticles
b. Quantum dot.
d. Carbon nanotubes
• Are being used for industrial applications in coatings,
cosmetics, pharmaceutical, and biomedical products.
• Recent studies have shown that nanostructured materials
impose significant risks to human health.
• Nanoparticles, being smaller in size (1–100 nm), can deposit
within the respiratory tract during inhalation.
• Once in the lungs, these nanoparticles start interacting with
different biological systems.The inhaled nanoparticles may have
toxic effects and could lead to lung diseases.
• For example, Amorphous silica is an important material for its
applications in biomedical research because it can be easily
produced at low cost .
• But, few reports have recently appeared showing that
amorphous silica may be toxic at relatively high doses.
Comparatively, a silica-chitosan nanocomposite causes less
inhibition in cell proliferation and less membrane.
• That means, the cytotoxicity of silica to human cells could be
reduced by using silica with chitosan.
• For Fe3O4, Al2O3, and TiO2 had no measurable effect on the cells
until the concentrations reached greater than 200 µg/ml.
• But more 200 µg/ml doses has been found that nanostructured
TiO2 particles could generate lung tumor and pulmonary fibrosis
• Fig 1. (A) to (C) images shows the morphology of mouse C18-4
spermatogonial stem cells by phase contrast microscopy after
incubation with different types of nanoparticles for 48 h. Fig. A is a
control specimen, Fig. B silver nanoparticles (15 nm Ag, 10 µg/ml),
some cells retain an intact plasma membrane (arrows), indicating
apoptosis. For fig C with Aluminum nanoparticles (30 nm Al, 10
µg/ml), the cytoplasm is clearly observed without apoptosis and
• Fullerenes are a very important class of carbonbased
nanostructured materials. The most common is a
buckminsterfullerene (buckyballs), C60.
• C60 itself shows limited solubility in organic solvents but its
solubility has been increased by chemical modification and
functionalization, therefore, derivatized fullerenes have opened
an avenue in the field of biological sciences including possible use
in the pharmaceuticall industry.
• For example, C60-containing bilayer lipid membranes may be
useful in a biosensor.
• In toxicity behavior, Yamago et al. stated when used a
radiolabeled fullerene with C14 and found fast migration, with
liver as the major target organ. It has been reported that fullerene
derivatives could even pass through the blood–brain barrier/
• C60 having the least degree of derivatization was more toxic to
cells. also shows that the toxicity of C60 based materials depends
upon the degree of surface functionalization.
Table 1: Cytotoxicity of fullerene-based nanostructured materials.
• CNTs can be prepared into single-walled (SW)-, double-walled
(DW)-, few-walled (FW), and multi-walled (MW) nanotubes.
• Carbon nanotubes (CNTs) are among the strongest and stiffest
• Single-w alled carbon nanotubes (SWCNTs) show potential for
applications in sensors, drug delivery systems, pharmaceutics,
electronics, photonics, display devices, reinforced composites,
• The biocompatibility and toxicity of carbon nanotubes has been
studied in experimental animals and humans.
• Liopo et al. stated that single-walled carbon nanotubes
(SWCNTs) can support neuronal attachment and growth by
• For the toxicity, Sharma et al. examined the toxicity of SWCNTs
in rat lung epithelial cells. Lung epithelial cells (LE cells) were
cultured with or without SWCNTs and reactive oxygen species
(ROS) were measured by change in fluorescence.
• Exposure to SWCNTs caused oxidative stress in LE cells and
showed loss of antioxidants.
• When, multiwall carbon nano-onions (MWCNOs) and multi-
walled carbon nanotubes (MWCNTs) on human skin. Shows
that’s, exposure increased apoptosis/necrosis effect.
• Fig. 7. Biodistribution histogram of 125I-SWNTols (352×106
cpm/ml, µ15 g/ml) in mice at eight different time intervals.
• Quantum dots have been used as a fluorescent labeling agents for
both in vitro and in vivo studies for stem cell labeling, medical
imaging , sensors, light-emittingdiodes, in vivo imaging,199 200
biological sensing, and multiplexing gene analysis.
• Recently, cytotoxicity of quantum dots (QDs) and deleterious
effects of the labeling procedure on human mesenchymal stem
cells has been reported.
• The cadmium-based quantum dots (QDs) showed cytotoxic effects.
• The CdTe quantum dots induce cell death by involving both Cd2+
and reactive oxygen species (ROS) accompanied by lysosomal
enlargement and intracellular redistribution
• Mainly released-diesel exhaust and petroleum
• Carcinogenic-radiation that is an agent directly
involved in causing cancer
• Consist 36-44% of the total concentration.
• Cytotoxicity is the quality of being toxic to cell.
Examples of toxic agents are a chemical substance,
an immune cells or some types of venom.
1. Apoptosis-(multicellular organism- include cell
shrinkage, nuclear fragmentation, and chromosomal
2. Necrosis-(external to the cell or tissue, such as
infection, toxins, or trauma that can lead to fatal.)
3. ROS generation-(Reactive oxygen species-oxidative
stress, ionizing radiation.)
4. Plasma membrane damage.
5. Cellular senescence-(normal diploid cells lose the
ability to divide, DNA double strand breaks due to
APPROACHES FOR INCREASING
BIOCOMPATIBILITY AND REDUCING
NANOTOXICITY OF NANOSTRUCTURED
What is nanotoxicology
• Nanotoxicology is the study of the toxicity of
nanomaterials. Because of quantum size effects
and large surface area to volume ratio,
nanomaterials have unique properties
compared with their larger counterparts.
• Nanotoxicology is a branch of bionanoscience
which deals with the study and application of
toxicity of nanomaterials.
• Toxic effects of nanostructured materials
could be reduced by using different
• Surface treatment and functionalization
of nanomaterials could help in reducing
toxic effects on human health.
• Cytotoxicity of quantum dots depends on
physicochemical and environmental
• The cytotoxicity of nanomaterials
depends upon their surface chemistry
and surface characteristics
• Cytotoxicity is studied in vitro, which may
not accurately indicate the comparative
toxicity in vivo.
• Nanoparticles may have adverse effects
on biological systems.
• In vitro: is a studies in experimental
biology on an organism that isolated from
their component which will done on the
out side, (test tube experiment).
• Can be focus on the cell of the organism,
so the result will be more accurately.
• But, in “in vitro” technique there is a few
thing that must be alert such as the
result, because sometimes the result will
not be same with the real situation.
• In vivo: is a biological studies on a living
things either partial or dead organism.
• As example, nowadays there is a in vitro
research on HIV curing. Which still cannot
work on the living organism. So in vivo
still need to be done.
Increases in environmental exposure in air,
water or soil.
Like other pollutants, they may pass from
organism to organism.
Harmful effects on invertebrates and fish,
including effects on behaviour,
reproduction and development.
The main focus is on micro-organisms and
invertebrates and studies on fish.
The hazardous effects include:
Growth and development
How to work safely with
Based on particle physics and studies of fine atmospheric
pollutants, the nanoparticle size range is the range of minimum
settling. This means that once released into air, nanoparticles
will remain airborne for considerable periods of time.
Nanoparticles can be inhaled and will be collected in all
regions of the respiratory tract; about 35% will deposit in the
deep region of the lungs.
Because they are so small, nanoparticles follow
airstreams more easily than larger particles, so they
will be easily collected and retained in standard
ventilated enclosures such as fume hoods. In addition,
nanoparticles are readily collected by HEPA filters.
Respirators with HEPA filters will be adequate
protection for nanoparticles in case of spills of large
amounts of material.
•Working safely with nanomaterials involves following standard
(MSDS) - preventing inhalation, skin contact, and ingestion.
•Many nanomaterials are synthesized in enclosed reactors or glove
•The enclosures are under vacuum or exhaust ventilation, which
prevent exposure during the actual synthesis.
•Inhalation exposure can occur during additional processing of
materials removed from reactors, this processing should be done in
•In addition, maintenance on reactor parts that may release residual
particles in the air should be done in fume hoods.
•Another process, the synthesis of particles using sol-gel chemistry,
should be carried out in ventilated fume hoods or glove boxes.