Transcript Nanoparticles - Springer Static Content Server

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Contents:
Medical Nanomachines and
Nanorobots
Nanoparticles in Medicine
Functions and Properties of Medical
Nanodevices
Removing Used Nanorobots
Conclusion
Medical Nanomachines and
Nanorobots
• Nanorobots are defined as nanomachines
capable of operating with nanosized objects and
with nanoscale precision.
• Nanorobots are also known as nanobots,
nanoids, nanites, nanomachines or nanomites.
• Medical nanomachines are designed to perform
single or repetitive tasks in biological cells with
nanoscale resolution.
Main Components of a Typical
Nanorobot
• Payload – A vacant portion in a nanorobot design that reserves a
small dose of drug/medicine for onward delivering to an
infection/injury site as it moves in the blood.
• A power source – Supplier of energy for nanodevice operation and
functions. Two types of energy sources are available for
nanomachines: external and internal power sources.
• Swimming tail – Needed for traversing through the body.
• Motor and manipulator arms/mechanical legs – Structures used
for different types of movements of nanomachines.
• Signal receiver and transmitter – A nanorobot must have the
ability to communicate that allows a human to physically guide the
robot as it transverses the body.
Examples of Current Medical
Nanodevices
• Three-dimensional DNA crystal, nanovalves for
drug delivery, molecular propellers, nanochips,
DNA nanorobots, nanorobots treating hepatitis
C, etc.
• A three-dimensional DNA crystal is an
assembly of synthetic DNA molecules forming
3D crystal structures capable of hosting guest
structures. These porous crystals can be used as
molecular containers to build biochips,
nanorobots, biodegradable solid-state catalysts
and biosensors, or for delivery of enzymes in
enzyme replacement therapies.
Examples of Current Medical
Nanodevices (continued)
• Nanovalves for drug delivery are tiny valves placed in the pores
of nanostructures, for example mesoporous silica nanoparticles,
filled by drug for controlled release of drugs. The nanovalves
open and close in response to change of pH level in the cellular
environment.
• Molecular propellers are special shaped molecules having several
molecular-scale blades tilted at a different pitch angle around the
rotational axis. The molecular propellers are able to push and
pump fluids when rotate by using the molecular motors.
Nanochips are used for DNA sequences analysis – DNA
hybridization, which is a process of pairing of separated DNA
strands with complementary strands of known sequence. These
strands act as probes. Nanochips use electric current to separate
DNA probes.
Nanoparticles in Medicine
• Nanoparticles are tiny particles of matter made of
any material (metal, semiconductor, glass, polymer,
organic, liquid or combination of different materials)
of any shape (nanosphere, nanoshell, nanorod,
nanotube, buckyball) and structure (solid, porous,
bubble, bilayer etc.) in the size range 1–100 nm,
designed to perform various functions and
manipulation of matter at this length scale.
• They are divided into two broad types: inorganic
material-based nanoparticles and organic materialbased nanoparticles.
Nanoparticles in Medicine
(continued)
• Nanoparticles used in medicine of either material type
have three distinct components of their design: the core,
which is used to hold the drug being administered, the
shell, which protects the particle from being rejected by the
body, and an external surface covering of a targeting agent
or drug to allow longer circulation in the body.
• Inorganic nanoparticles can be used to induce
hyperthermia of cells, and magnetic fields can be used to
guide magnetic nanoparticles once injected into the body.
• Examples of the most commonly used inorganic particles
are: the metallic nanoparticles, nanowires, fullerenes,
carbon nanotubes, silica shells, and quantum dots.
Metallic Nanoparticles
• Metallic nanoparticles are mostly made of noble metals, like gold,
silver and platinum, or metal oxides, like iron oxide, nickel oxide and
cobalt oxide, and have a wide variety of applications in diagnostics and
therapy. .
• Imaging modalities used in clinics today (MRI, CT, PET and optical
imaging) require contrast agents with specific morphological properties.
By using metal nanoparticles of a specific design, we can create
contrast enhancers that locate themselves strictly on cells of interest
(through fine-tuned targeting agents) and also last longer, allowing us to
watch the growth, death or movement of tumor cells over a longer
period of time.
• The metal nanoparticles are used in the therapy of cancer. Two therapies,
nanophotothermolysis and nanophotohyperthermia, both utilize
molecular-targeting to deliver nanoparticles to a localized area, and then
use the unique light-absorption properties of the metal nanoparticles to
generate heat in the targeted region to ablate the tumor.
Carbon Nanoparticles
• Fullerene is the fourth allotrope of carbon, consisting of 60
carbon atoms forming specific spherical shape, buckyball. Its
unique properties, such as heat resistance and
superconductivity, enable applications in high-temperature
superconducting materials, high-power optical materials, highperformance catalyst, and high-strength composite materials.
• Carbon nanotubes are arrangements of planar carbon lattices
into cylinders of various chiralities with sizes reaching several
millimeters in length and only a few nanometers wide. In
biology, the ability of nanotubes to get inside cell nuclei makes
them invaluable in the diagnosis, imaging and treatment
phases of cancer therapy. Carbon nanotube can be used to
recognize target DNA sequences, as a drug delivery system,
used in artificial heart valves, tooth roots, bones, etc.
Silica-Based Nanoparticles
• Silica-based nanoparticles (SiNPs) made of silicon dioxide have
uniform morphology, adjustable pore volume, controllable
diameter, modifiable surface potential, easy functionalization and
synthesis.
• There are two types of silicon nanoparticles, mesoporous
(MSNs) and core/shell nanoparticles (C/S-SiNPs).
• MSNs have been successfully used for drug delivery because of
unique mesopores and nanochannels which allow for a high
payload of the drug and easy stimulated release.
• C/S-SiNPs, like silica-coated gold nanoparticles, are ideal for
imaging agent delivery because the agents used, such as
fluorophores, quantum dots and gold nanoparticles, can be easily
doped into the C/S-SiNPs.
Quantum Dots
• Quantum dots are another example of inorganic nanoparticles
that can be used for the purpose of increased imaging ability.
• These dots are small semiconductor crystals that we can be finetuned to have very specific spectral bands, allowing
differentiation between the location of the quantum dot (on the
tumor cell) and the healthy tissue beside it with a level of
precision not possible before.
• The labeling of multiple disease markers with quantum dotbased barcodes could pave the way towards more sensitive and
accurate disease detection systems. Quantum dot-based probes
may be used to study the heterogeneity of disease markers and
link them to prognosis for improved diagnostic strategies.
Organic Particles
• Organic particles are used primarily for drug delivery or as a
coating on inorganic particles to assure they are not rejected by the
body’s immune system.
• Examples include polymer-based nanostructures, dendritic
nanoparticles, liposome nanoparticles, polymersome
nanoparticles, lipid formulations, micelle nanoparticles,
nanoemulsions, alginates, biological nanoparticles,etc.
• Polymer-based nanostructures are created from conjugating
several functional units and soluble macromolecules or by copolymer self-assembly. Many of these structures are loaded with
therapeutic or imaging agents which, through diffusion or
stimulation of the local environment, control the release. Polymeric
nanoparticles are a class of nanocarriers established for numerous
drug delivery applications.
Organic Particles (continued)
• A dendrimer nanoparticle is a type of polymeric nanostructure and
can be synthesized as well-defined spherical structure over 110
nm in diameter. A single dendrimer is able to sense, image and
perform therapeutic functions.
• Polymersome nanoparticles are drug delivery carriers having
structural similarity to liposomes and made of synthetic polymer
amphiphiles. These drug delivery systems have higher stability and
higher fluidity on the sides/surface than liposomes.
• Lipid formulations. There are many types of lipid-based drug
delivery systems. Such vehicles typically are comprised of a
digestible lipid with a blend of surfactants, co-surfactants and
potentially co-solvents.
Organic Particles (continued)
• Micelle nanoparticles are drug delivery carriers made up of lipids.
They are self-assembled into small nanoparticles having a
hydrophobic core (drug) within the size range 10200 nm.
• Biological nanoparticles are unicellular microorganisms with
different shapes and sizes. For example, a biological nanoparticle
called “nanocell” consists of globular bacteria having no nucleus,
which is impeccable, as it wouldn’t lead to mutations. A nanocell
can be filled by drug and used as a drug delivery system.
• Hybrid nanoparticles are nanocarriers made up of metallic and
polymeric materials for the central core, which is coated with
single or multiple layers of lipid to create a protective
(surrounding) membrane. These nanoparticles are used as delivery
systems with considerable high drug carrying capacity, and the
lipid layer on the surface of a nanoparticle is able direct drugreleasing kinetics.
Functions of Medical Nanodevices
• Medical nanomachines and nanoparticles are designed to
perform several functions in the biological environment with the
nanoscale precision.
• These functions can either be demonstrated individually or in
combinations.
• Some functions necessary for nanorobots include:
 Swarm intelligence – related to reorganization and distributive intelligence.
 Self-assembly and replication –refers to automated assembling and
reproduction ability of a nanorobot.
 Information processing – refers to programming ability of a nanorobot.
 Nano to macro world interaction – relates to a framework which enables
immediate access to the nanorobots.
Properties of Medical Nanodevices
• In order to perform these functions and activities in the body
environment the medical nanodevices should possess the following
properties:
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Special morphological properties: structure, shape and size
Surface chemistry
Moving and swimming ability
Biocompatibility
Powering
Communication
Navigation
• Morphological properties: structure, shape and size. The
geometry of the nanoparticle can be altered to affect its overall
properties. The optimum nanorbot shape depends on functions and
the environment wherein the nonodevice is designed to operate.
Morphological Properties of Medical
Nanodevices
• For example, free-floating nanodevices are nanorobots intended
as material delivery or storage devices operating independently
with no preferred orientation. Thus, the spherical shape offers the
best volume efficiency.
• Swimming nanodevices are designed to move effectively though
the blood stream. Less resistance to the surrounding fluids is
needed for actively-swimming nanodevices. It can be achieved for
smaller surface area in contact with fluid. The ellipsoid shape will
be ideal for this type of nanomachine.
• Intracellular nanodevices are designed to operate inside human
tissues and cells to carry payloads like drugs, nanocomputers,
power supplies, tools, communicational and navigational
equipment. The spherical shape provides a maximum volume for a
volume storage efficiency. The carbon nanotubes with cylindrical
shape are also considered to be effective nanocarriers.
Morphological Properties (continued)
• Tessellating nanomachines involve cooperation by other
nanodevices in close physical contact. They are designed to fit
together in a mosaic pattern. The triangles, hexagons and
polygonal prismatic shapes can provide a tight connection in
designed order.
• The shape of nanoparticles can be altered to affect its overall
properties. For example, the aspect ratio, i.e., ratio of length to the
width) of a gold nanorod particle affects its absorbance spectra,
which is much higher than the spherical-shaped gold nanoparticle
of approximately similar size.
• The geometry of the nanoparticle has also been shown to affect its
intake into the cells.
• The nanoparticle geometry can also affect its half-life in the blood.
The half-life is the amount of time it takes for the concentration of
nanoparticles in the blood to be reduced by 50%.
Structure of Nanoparticles
• The structure of nanoparticles can affect their overall properties
as well.
• Structurally the nanoparticles can be made as uniform core
particles, porous nanoparticles, nanoshells, and single and
multilayer nanoparticles with different surface chemistry.
• The nanoparticle core may be synthesized from a wide variety of
materials in different geometries and sizes. Materials such as
carbon in carbon nanotubes or gold in gold nanorods or silica and
gold in gold nanoshells have been used to deliver thermal therapy
to cancer cells.
• Nanoshells have big advantages over uniform core nanoparticles:
(1) nanoshells can contain strong drugs inside, and (2) their
absorption spectrum can be tuned to different wavelengths of
radiation by controlling the ratio of the thickness of the walls to the
overall diameter of the shell.
Surface Chemistry of Nanoparticles
• Surface chemistry on the surface of nanoparticles and
nanomachines plays an important role in targeting abnormal cells,
cell uptake, navigation of nanodevices, and selective drug delivery.
• The surface chemistry can increase the half-life time of
nanoparticles inside the body and thereby increase the availability
to the target cells.
• In addition, as the interface between the nanomaterial and the
biological environment, the surface chemistry largely determines
whether a nanoparticle suppresses or stimulates immune
responses. Without surface modification, nanoparticles have been
reported to be removed from the bloodstream within seconds by
macrophages cells which remove foreign objects and stimulate
other immune cells.
Size of Nanoparticles
• The size of nanoparticles plays a crucial role in the overall
properties of nanoparticles, their functions and applications.
• The particles under 100 nm in size can freely circulate around a
body, penetrate into the any organs, and can be effectively
collected at the tumor sites.
• For example, the overall size of the nanoparticle drug delivery
system may be tuned for delivery to the tumor site via tumor
vasculature and then to an intracellular target.
• The nanoparticle size can mediate the efficiency of its uptake into
cells. It has been shown that maximum cellular uptake is achieved
with 50 nm particles.
• Finally, smaller sized nanoparticles undergo better renal clearance
from the bloodstream after the targeted nanoparticle therapy.
Biocompatibility Property
• Biocompatibility refers to the property of a nanodevice being
biologically compatible by not causing any response from the
immune system of the body.
• The immune system rejects a “foreign” body. The outside surface
of the nanomachine/nanoparticles should not react with the body
chemistry in order to avoid rejection by the immune system.
• The nanorobot consists of two spaces – interior and exterior.
• The exterior surface of the nanodevice is exposed to the human
fluids. The interior space doesn’t interact with outside fluids.
• To achieve biocompatibility, it is enough to cover the external
surface of the nanodevice by inert materials like noble metals
(gold, platinum, silver). Also, the proteins found in the body are
good protective layers on the surface nanomachines, which are
recognized by the immune system.
Powering of Nanomachines
• Powering supplies energy for nanomachines to perform their
functions, mechanical motions, pumping, chemical
transformations, etc.
• There are two power sources are available for the operation of
nanorobots: internal and external.
• The internal power source relies on the heat of patient’s body,
which can be used directly as a temperature gradient or converted
into other forms of energy. A nanodevice can metabolize the
glucose and oxygen directly from bloodstream for energy.
• The external power can be delivered in the form of
electromagnetic radiation, which has high penetration into the
body. Examples include IR and RF radiation, magnetic field or
ultrasound waves.
Communication
• Communication with the outside world and between the
nanorobots is required to perform various functions inside the
body.
• One way to send messages into the body is RF messaging in the
1–10 MHz frequency range.
• Most of the cell communication uses chemical signals.
• The goal is to teach and make the nanorobots collaborate with each
other. Making a bionano swarm on a tumor is a great example.
• Designing a communication network for nanorobots is an
extremely challenging task. Nature has made systems or structures
which can do exactly that  viruses. The creation of nanotubes,
nanotransitors, nanophotonics, nanowires and nanowaveguides
is accelerating this giant step toward a fully operating nanorobots
Navigation of Nanodevices
• Navigation is another important property of nanomachines and is
divided into two categories: external systems and on-board
systems.
• External navigation systems are used to identify the location of a
nanorobot and direct it towards the exact target. Examples of such
a system include ultrasonic signals, magnetic field or
electromagnetic radiation.
• The ultrasonic signals would pass through body or reflect back.
• The MRI scanners can help to locate the nanorobots if they made
up of or covered by a magnetic material.
• On-board systems are used to reach specific target based on certain
chemicals and proteins on the surface of the nanorobot designed to
search for and stick to the receptors of the tumor cells only.
Removing Used Nanorobots
• Removing used nanorobots from a body is
provided by human excretory channels in
the natural way.
• After the devices have finished their job,
they will be flushed out from the body in a
few hours after injection.
• The removal time depends on the size,
shape, surface chemistry and concentration
of nanorobots.
Conclusions
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In conclusion, nanorobots used in nanomedicine hold a wealth of
promise. There are still many obstacles to overcome such as
design, electrical system, complicated interface and
communication, and networking.
There has also been an evolution of theories on nanomachines
derived from nanotechnology techniques as being self-replicating
to a more accepted ideology of a mechanical technique, which
calls for greater need of control over the biological processes.
Based on current theories, molecular nanotechnology is the big
concept that encompasses the fabrication of nanorobots. This
will be the beginning of a new age where various disciplines like
robotics, mechanical, chemical and biomedical engineering will
collaborate together in order to manufacture effusively functional
systems.