Post on 23-Jun-2020
NANOMATERIALS AND ADVANCED MATERIALS
PROCESSING : HEALTH IMPACT
Shaharum Shamsuddin D. Phil. (Oxon.)
Biomedicine Programme
School of Health Sciences USM
For East Coast Environmental Health Seminar,
USM Health Campus, (18-19 July 2012)
NANOTECHNOLOGY
Nanotechnology involve research in the level of 100 nm and
below in at least one dimension
10-1 nm 100 nm 101 nm 103 nm 102 nm 10 4 nm > 10 5 nm
H2O Protein Ribosomes Nuclearpore
Mitochondrion
Cells Tissues
Comparisons of biological molecules found in nature with
representative sizes of `small’ object of man made Nanomaterials
NANOCARRIERS :
• Made from a material that is biocompatible,
• Well characterized, and easily functionalized;
• Exhibit high differential uptake efficiency in the target cells
• Soluble or colloidal under aqueous conditions for increased
effectiveness
• Have an extended circulating half-life,
• A low rate of aggregation
• A long shelf life.
NANOCARRIER ADVANTAGES
• Protect the drug from premature degradation;
• Prevent drugs from prematurely interacting with the biological
environment
• Enhance absorption of the drugs into a selected tissue (for example,
solid tumour);
• Control the pharmacokinetic and drug tissue distribution profile;
• Improve intracellular penetration.
NANOTOXICOLOGY IS IN ITS INFANCY
Do the unique material properties of nanomaterials equate to unique
biological properties as well?
Which of these properties are responsible for the biological effects?
Are the effects limited by the traditional defintion of nanomaterial (1-100 nm)?
Who should be studying the biocompatibility or toxicity of these new
materials?
What studies should be done?
APPLICATION OF NANOTECHNOLOGY IN MEDICINE
1 Khairunisak Abdul Razak
2 Azlan Abdul Aziz 3 Shaharum Shamsuddin 4 Laurent Levy
1 School of Material Science & Mineral Engineering (Engineering campus USM)
2 School of Physics (Main Campus,)
3School of Health Sciences (Health Campus)
4Nanobiotix SA, 60 rue De Wattignies, 75012 Paris, France
Nanobiotechnology Research & Innovation , Institute for Molecular Medicine (INFORMM)
(NanoBRI @ INFORMM)
UNIVERSITI SAINS MALAYSIA
TIMELINE OF NANOTECHNOLOGY VS LIFE SCIENCE & MEDICINE
The development of nanomaterial for human use must follow a very strict regulation
Seven challenges (Sanhai et al., 2008)
1. Determination of the distribution of NP in the body following
systemic administration
2. Development of imaging modalities for visualizing the distribution
over time
3. Understanding of mass transport across compartment boundaries
in the body (how NP negotiate with biological barriers)
4. The need to predict the risk of NP (will be discuss in next slide)
5. The need to predict the benefit of NP
6. Establishment of standard/reference material & consensus
protocol that can provide benchmark for the development of novel
classes of materials
7. Realization of an analytical tool kit for Nanopharmaceutical
manufacturing + specs sheet of toxicology, safety & biodistribution
properties obtained via standardized, validated methods
NANOTOXICITY…
- An emerging important sub-discipline in
Nanotechnology
- The study of the interaction of the
nanostructure with biological system
- How it can induce toxic biological response
KIND OF TOXICITY…
Type of Nanoparticles
Nanosilica
Nanomagnetic
NanoGold
Liposomes
Polymers
TiO2
Publication & Patent Boom
Nanotechnology publications and patents worldwide. Source :
Wagner et al., (2006). Nature Biotechnology Vol. 24, No. 10, pp 1211 - 1217
NANOTOXICOLOGY IS IN ITS INFANCY
236 January ‘08
Comparison of nanoparticle uptake as a function of size reported by (A) Chithrani et al. (2006) and (B) Lu et al.
(2009). (C) The results of Chithrani et al. (2006) are re-plotted with the particle uptake expressed in pg/cell,
instead of number of particles per cell
Nanoparticles uptake by the cells
Chithrani et.al.,. Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett
2006; 6: 6628.
Lu F, Wu SH, Hung Y, Mou CY. Size effect on cell uptake in well-suspended, uniform mesoporous silica nanoparticles.
Small 2009; 5: 1408-13.
The relationship between absorption, distribution, metabolism and
excretion (ADME) to detoxication and toxicity of a chemical.
Potential biodistribution of particles
Comparison on pharmacokinetics and distribution model between
small molecules and nanoparticles
How Nanomaterial can be toxic to human – The Seven
challenges (Sanhai et al., 2008)
1. Determination of the distribution of NP in the body following
systemic administration
2. Development of imaging modalities for visualizing the distribution
over time
3. Understanding of mass transport across compartment boundaries
in the body (how NP negotiate with biological barriers)
4. The need to predict the risk of NP (will be discuss in next slide)
5. The need to predict the benefit of NP
6. Establishment of standard/reference material & consensus
protocol that can provide benchmark for the development of novel
classes of materials
7. Realization of an analytical tool kit for Nanopharmaceutical
manufacturing + specs sheet of toxicology, safety & biodistribution
properties obtained via standardized, validated methods
Risk analysis is another important tool prior to scale up. The above figure
shows example of risk analysis of nanomaterial fabrication
Cellular Toxicity of Nanoparticle [ROS products such as superoxide (•O2-) and hydroxyl radical (•OH)]
(Event 1 - Cell membrane integrity leading to cell survivability will
be affected by ROS produced by a nanoparticle smaller than a
cell (red particle) as shown). Event 2 represents the situation
where a nanoparticle is internalized and then creates ROS
products. In Event 3, particle dissolution affect cellular function
after nanoparticle internalization while Event 4 represent any
mechanical damage to sub-cellular units such as the lysosome,
endoplasmic reticulum and nucleus itself. In Event 5, different
functional groups and surface electronic structures arising from
different nanostructured materials can determine the level of
interaction between the nanoparticles and their surroundings.
Overall size of the particle can play an important role as
represented by Event 6 since large particles can potentially
induce permanent damage to the cell membrane while small
particles can pass through the membrane and do harm inside
cell. Even 7 involved non-spherical particles which might have a
different biological response compared to the spherical
nanoparticles. Event 8 dissolutionn of NP into the cell may effect
the cell in various way
Important of Toxicity study (in vitro & in vivo)
Potential targets include:
- Liver and organs of the
reticuloendothelial system (RES)
- Kidney (e.g.: possibility of
urolithiasis, tubular lesions),
- Central nervous system (thru BBB)
- Reproductive organs
- Cardiovascular system (e.g.:
formation of aggregates),
- Development of inflammatory
reactions, which appear to constitute
a major risk for the respiratory tract,
related to the formation of
agglomerates
Nanotoxicity impact on human health (cont.)
Summary diagrams showing the possible areas of localization of nanoparticles to various tissues from the
blood circulation. Opsonization can result in uptake to the liver, but changes in size or surface
characteristics can result in accumulation in a wide range of other tissues.
Nanoparticles in vivo distribution : USM experience
Rifampicin + DID (fluorescence dye) encapsulate in Nanosilica particle
NanoDiD
NanoDiD + Rif DiD control mouse
Conclusion : Target organ for Nanosilica : Uterus-Ovary,
Liver, Muscle, Skin & Lung
Nanoparticles into the cells : Difficulties
1. Very few comprehensive quantitative studies of the kinetics of interaction
and uptake of nanomaterials into the cells – Time for saturation of
equilibrium, size/shape dependent ?
2. How to know exactly which species are taken up by the cell. Is it single
nanoparticles or aggregates formed prior to, or during interaction with the
membrane? Does functionalization of surface play important role ?
3. Passive uptake of nanomaterials always results in endosomal localization.
This is a stringent limitation for biological and biomedical applications and
therefore considerable efforts need to be done to escape/bypass the
endocytotic pathway
TERIMA KASIH