Nanomedicine is the medical application of nanotechnology. Nanomedicine ranges from the medical applications of nanomaterials and biological devices, to nanoelectronic biosensors, and even possible future applications of molecular nanotechnology such as biological machines. Current problems for nanomedicine involve understanding the issues related to toxicity and environmental impact of nanoscale materials (materials whose structure is on the scale of nanometers, i.e. billionths of a meter).
A ribosome is a biological machine.
Functionalities can be added to nanomaterials by interfacing them
with biological molecules or structures. The size of nanomaterials is
similar to that of most biological molecules and structures; therefore,
nanomaterials can be useful for both in vivo and in vitro biomedical
research and applications.
Thus far, the integration of nanomaterials with biology has led to the
development of diagnostic devices, contrast agents, analytical tools,
physical therapy applications, and drug delivery vehicles.
Nanomedicine seeks to deliver a valuable set of research tools and clinically useful devices in the near future. The National Nanotechnology Initiative expects new commercial applications in the pharmaceutical industry that may include advanced drug delivery systems, new therapies, and in vivo imaging. Nanomedicine research is receiving funding from the US National Institutes of Health Common Fund program, supporting four nanomedicine development centers.
Nanomedicine sales reached $16 billion in 2015, with a minimum of
$3.8 billion in nanotechnology R&D being invested every year.
Global funding for emerging nanotechnology increased by 45% per year in
recent years, with product sales exceeding $1 trillion in 2013. As the nanomedicine industry continues to grow, it is expected to have a significant impact on the economy.
Drug delivery
Nanoparticles (top), liposomes (middle), and dendrimers (bottom) are some nanomaterials being investigated for use in nanomedicine.
Nanotechnology has provided the possibility of delivering drugs to specific cells using nanoparticles.
The overall drug consumption and side-effects may be lowered
significantly by depositing the active agent in the morbid region only
and in no higher dose than needed. Targeted drug delivery is intended to
reduce the side effects of drugs with concomitant decreases in
consumption and treatment expenses. Drug delivery focuses on maximizing bioavailability
both at specific places in the body and over a period of time. This can
potentially be achieved by molecular targeting by nanoengineered
devices.
A benefit of using nanoscale for medical technologies is that smaller
devices are less invasive and can possibly be implanted inside the body,
plus biochemical reaction times are much shorter. These devices are
faster and more sensitive than typical drug delivery.
The efficacy of drug delivery through nanomedicine is largely based
upon: a) efficient encapsulation of the drugs, b) successful delivery of
drug to the targeted region of the body, and c) successful release of
the drug.
Drug delivery systems, lipid- or polymer-based nanoparticles, can be designed to improve the pharmacokinetics and biodistribution of the drug. However, the pharmacokinetics and pharmacodynamics of nanomedicine is highly variable among different patients. When designed to avoid the body's defense mechanisms,
nanoparticles have beneficial properties that can be used to improve
drug delivery. Complex drug delivery mechanisms are being developed,
including the ability to get drugs through cell membranes and into cell cytoplasm.
Triggered response is one way for drug molecules to be used more
efficiently. Drugs are placed in the body and only activate on
encountering a particular signal. For example, a drug with poor
solubility will be replaced by a drug delivery system where both
hydrophilic and hydrophobic environments exist, improving the
solubility.
Drug delivery systems may also be able to prevent tissue damage through
regulated drug release; reduce drug clearance rates; or lower the
volume of distribution and reduce the effect on non-target tissue.
However, the biodistribution of these nanoparticles is still imperfect
due to the complex host's reactions to nano- and microsized materials
and the difficulty in targeting specific organs in the body.
Nevertheless, a lot of work is still ongoing to optimize and better
understand the potential and limitations of nanoparticulate systems.
While advancement of research proves that targeting and distribution can
be augmented by nanoparticles, the dangers of nanotoxicity become an
important next step in further understanding of their medical uses.
Nanoparticles are under research for their potential to decrease antibiotic resistance or for various antimicrobial uses. Nanoparticles might also be used to circumvent multidrug resistance (MDR) mechanisms.
Systems under research
Advances
in lipid nanotechnology were instrumental in engineering medical
nanodevices and novel drug delivery systems, as well as in developing
sensing applications. Another system for microRNA delivery under preliminary research is nanoparticles formed by the self-assembly of two different microRNAs deregulated in cancer. One potential application is based on small electromechanical systems, such as nanoelectromechanical systems
being investigated for the active release of drugs and sensors for
possible cancer treatment with iron nanoparticles or gold shells.
Applications
Some nanotechnology-based drugs that are commercially available or in human clinical trials include:
- Abraxane, approved by the U.S. Food and Drug Administration (FDA) to treat breast cancer, non-small- cell lung cancer (NSCLC) and pancreatic cancer, is the nanoparticle albumin bound paclitaxel.
- Doxil was originally approved by the FDA for the use on HIV-related Kaposi's sarcoma. It is now being used to also treat ovarian cancer and multiple myeloma. The drug is encased in liposomes, which helps to extend the life of the drug that is being distributed. Liposomes are self-assembling, spherical, closed colloidal structures that are composed of lipid bilayers that surround an aqueous space. The liposomes also help to increase the functionality and it helps to decrease the damage that the drug does to the heart muscles specifically.
- Onivyde, liposome encapsulated irinotecan to treat metastatic pancreatic cancer, was approved by FDA in October 2015.
Cancer
Preclinical research
Existing and potential drug nanocarriers have been reviewed.
Nanoparticles have high surface area to volume ratio. This allows
for many functional groups to be attached to a nanoparticle, which can
seek out and bind to certain tumor cells.
Additionally, the small size of nanoparticles (5 to 100 nanometers),
allows them to preferentially accumulate at tumor sites (because tumors
lack an effective lymphatic drainage system). Limitations to
conventional cancer chemotherapy include drug resistance, lack of
selectivity, and lack of solubility.
Imaging
In vivo imaging is another area where tools and devices are being developed. Using nanoparticle contrast agents,
images such as ultrasound and MRI have a favorable distribution and
improved contrast. In cardiovascular imaging, nanoparticles have
potential to aid visualization of blood pooling, ischemia, angiogenesis, atherosclerosis, and focal areas where inflammation is present.
The small size of nanoparticles endows them with properties that can be very useful in oncology, particularly in imaging.
Quantum dots (nanoparticles with quantum confinement properties, such
as size-tunable light emission), when used in conjunction with MRI
(magnetic resonance imaging), can produce exceptional images of tumor
sites. Nanoparticles of cadmium selenide glow when exposed to ultraviolet light. When injected, they seep into cancer tumors.
The surgeon can see the glowing tumor, and use it as a guide for more
accurate tumor removal.These nanoparticles are much brighter than
organic dyes and only need one light source for excitation. This means
that the use of fluorescent quantum dots could produce a higher contrast
image and at a lower cost than today's organic dyes used as contrast media.
The downside, however, is that quantum dots are usually made of quite
toxic elements, but this concern may be addressed by use of fluorescent
dopants.
Tracking movement can help determine how well drugs are being
distributed or how substances are metabolized. It is difficult to track a
small group of cells throughout the body, so scientists used to dye the
cells. These dyes needed to be excited by light of a certain wavelength
in order for them to light up. While different color dyes absorb
different frequencies of light, there was a need for as many light
sources as cells. A way around this problem is with luminescent tags.
These tags are quantum dots attached to proteins that penetrate cell membranes.
The dots can be random in size, can be made of bio-inert material, and
they demonstrate the nanoscale property that color is size-dependent. As
a result, sizes are selected so that the frequency of light used to
make a group of quantum dots fluoresce is an even multiple of the
frequency required to make another group incandesce. Then both groups
can be lit with a single light source. They have also found a way to
insert nanoparticles
into the affected parts of the body so that those parts of the body
will glow showing the tumor growth or shrinkage or also organ trouble.
Sensing
Nanotechnology-on-a-chip is one more dimension of lab-on-a-chip
technology. Magnetic nanoparticles, bound to a suitable antibody, are
used to label specific molecules, structures or microorganisms. In
particular silica nanoparticles are inert from the photophysical point
of view and might accumulate a large number of dye(s) within the
nanoparticle shell. Gold nanoparticles tagged with short segments of DNA
can be used for detection of genetic sequence in a sample. Multicolor
optical coding for biological assays has been achieved by embedding
different-sized quantum dots into polymeric microbeads. Nanopore technology for analysis of nucleic acids converts strings of nucleotides directly into electronic signatures.
Sensor test chips containing thousands of nanowires, able to
detect proteins and other biomarkers left behind by cancer cells, could
enable the detection and diagnosis of cancer in the early stages from a
few drops of a patient's blood. Nanotechnology is helping to advance the use of arthroscopes,
which are pencil-sized devices that are used in surgeries with lights
and cameras so surgeons can do the surgeries with smaller incisions. The
smaller the incisions the faster the healing time which is better for
the patients. It is also helping to find a way to make an arthroscope
smaller than a strand of hair.
Research on nanoelectronics-based cancer diagnostics could lead to tests that can be done in pharmacies.
The results promise to be highly accurate and the product promises to
be inexpensive. They could take a very small amount of blood and detect
cancer anywhere in the body in about five minutes, with a sensitivity
that is a thousand times better a conventional laboratory test. These
devices that are built with nanowires to detect cancer proteins; each nanowire detector is primed to be sensitive to a different cancer marker.
The biggest advantage of the nanowire detectors is that they could test
for anywhere from ten to one hundred similar medical conditions without
adding cost to the testing device.
Nanotechnology has also helped to personalize oncology for the
detection, diagnosis, and treatment of cancer. It is now able to be
tailored to each individual’s tumor for better performance. They have
found ways that they will be able to target a specific part of the body
that is being affected by cancer.
Blood purification
Magnetic
micro particles are proven research instruments for the separation of
cells and proteins from complex media. The technology is available under
the name Magnetic-activated cell sorting or Dynabeads among others. More recently it was shown in animal models that magnetic nanoparticles can be used for the removal of various noxious compounds including toxins, pathogens, and proteins from whole blood in an extracorporeal circuit similar to dialysis. In contrast to dialysis, which works on the principle of the size related diffusion of solutes and ultrafiltration of fluid across a semi-permeable membrane,
the purification with nanoparticles allows specific targeting of
substances. Additionally larger compounds which are commonly not
dialyzable can be removed.
The purification process is based on functionalized iron oxide or carbon coated metal nanoparticles with ferromagnetic or superparamagnetic properties. Binding agents such as proteins, antibodies, antibiotics, or synthetic ligands are covalently
linked to the particle surface. These binding agents are able to
interact with target species forming an agglomerate. Applying an
external magnetic field
gradient allows exerting a force on the nanoparticles. Hence the
particles can be separated from the bulk fluid, thereby cleaning it from
the contaminants.
The small size (< 100 nm) and large surface area of functionalized nanomagnets leads to advantageous properties compared to hemoperfusion, which is a clinically used technique for the purification of blood and is based on surface adsorption.
These advantages are high loading and accessible for binding agents,
high selectivity towards the target compound, fast diffusion, small
hydrodynamic resistance, and low dosage.
This approach offers new therapeutic possibilities for the treatment of systemic infections such as sepsis by directly removing the pathogen. It can also be used to selectively remove cytokines or endotoxins
or for the dialysis of compounds which are not accessible by
traditional dialysis methods. However the technology is still in a
preclinical phase and first clinical trials are not expected before
2017.
Tissue engineering
Nanotechnology may be used as part of tissue engineering
to help reproduce or repair or reshape damaged tissue using suitable
nanomaterial-based scaffolds and growth factors. Tissue engineering if
successful may replace conventional treatments like organ transplants or
artificial implants. Nanoparticles such as graphene, carbon nanotubes,
molybdenum disulfide and tungsten disulfide are being used as
reinforcing agents to fabricate mechanically strong biodegradable
polymeric nanocomposites for bone tissue engineering applications. The
addition of these nanoparticles in the polymer matrix at low
concentrations (~0.2 weight %) leads to significant improvements in the
compressive and flexural mechanical properties of polymeric
nanocomposites. Potentially, these nanocomposites may be used as a novel, mechanically strong, light weight composite as bone implants.
For example, a flesh welder was demonstrated to fuse two pieces
of chicken meat into a single piece using a suspension of gold-coated nanoshells activated by an infrared laser. This could be used to weld arteries during surgery.
Another example is nanonephrology, the use of nanomedicine on the kidney.
Medical devices
Neuro-electronic
interfacing is a visionary goal dealing with the construction of
nanodevices that will permit computers to be joined and linked to the
nervous system. This idea requires the building of a molecular structure
that will permit control and detection of nerve impulses by an external
computer. A refuelable strategy implies energy is refilled continuously
or periodically with external sonic, chemical, tethered, magnetic, or
biological electrical sources, while a nonrefuelable strategy implies
that all power is drawn from internal energy storage which would stop
when all energy is drained. A nanoscale enzymatic biofuel cell for self-powered nanodevices have been developed that uses glucose from biofluids including human blood and watermelons.
One limitation to this innovation is the fact that electrical
interference or leakage or overheating from power consumption is
possible. The wiring of the structure is extremely difficult because
they must be positioned precisely in the nervous system. The structures
that will provide the interface must also be compatible with the body's
immune system.
Molecular nanotechnology is a speculative subfield of nanotechnology regarding the possibility of engineering molecular assemblers, machines which could re-order matter at a molecular or atomic scale. Nanomedicine would make use of these nanorobots,
introduced into the body, to repair or detect damages and infections.
Molecular nanotechnology is highly theoretical, seeking to anticipate
what inventions nanotechnology might yield and to propose an agenda for
future inquiry. The proposed elements of molecular nanotechnology, such
as molecular assemblers and nanorobots are far beyond current capabilities. Future advances in nanomedicine could give rise to life extension through the repair of many processes thought to be responsible for aging. K. Eric Drexler,
one of the founders of nanotechnology, postulated cell repair machines,
including ones operating within cells and utilizing as yet hypothetical
molecular machines, in his 1986 book Engines of Creation, with the first technical discussion of medical nanorobots by Robert Freitas appearing in 1999. Raymond Kurzweil, a futurist and transhumanist, stated in his book The Singularity Is Near that he believes that advanced medical nanorobotics could completely remedy the effects of aging by 2030. According to Richard Feynman, it was his former graduate student and collaborator Albert Hibbs who originally suggested to him (circa 1959) the idea of a medical use for Feynman's theoretical micromachines (see nanotechnology).
Hibbs suggested that certain repair machines might one day be reduced
in size to the point that it would, in theory, be possible to (as
Feynman put it) "swallow the doctor". The idea was incorporated into Feynman's 1959 essay There's Plenty of Room at the Bottom.
