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Sam Bath 13SO
How hasthe introductionof nanotechnologyaidedthe developmentof cancertreatments?
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How has the introduction of nanotechnology aided the
development of cancer treatments?
What is nanotechnology?
The ideas and concepts behind nanotechnology (and nanoscience in general) all started
with a talk entitled “There’s Plenty of Room at the Bottom” by physicist Richard
Feynman at the California Institute of Technology on December 29, 1959. This was long
before the term nanotechnology was used. In his talk, Feynman described a process in
which scientists would be able to manipulate and control individual atoms and
molecules. It was over a decade later, in his explorations of ultraprecision machining,
that Professor Norio Taniguchi created the term nanotechnology. It wasn't until 1981,
with the development of the scanning tunneling microscope that could "see" individual
atoms that modern nanotechnology truly began.
It’s hard to imagine just how small the scales of nanotechnology are. One nanometer is a
billionth of a meter, or 10-9 of a meter. For example, there are 25,400,000 nanometers in
an inch. Furthermore, a sheet of newspaper is about 100,000 nanometers thick. Scaled
up on a comparative scale, if one nanometer represented the diameter of a marble,
then a ball with a diameter representing one meter would be the size of the Earth.
More recently, the opportunities that nanotechnology can bring to everyday life have
been exploited in greater detail, and to a wider range of applications. As well as being
introduced to areas such as the reduction of energy consumption, computing, aerospace
and chemical catalysis, nanotechnology has helped make some groundbreaking medical
breakthroughs. Chief among these is the advancements made in cancer treatments, for
it is in this field that nanotechnology plays the greatest role in offering more effective
diagnosis, prevention and treatment methods.
How are nanotechnology and cancer linked?
The National Cancer Institute has set a goal of eliminating death and suffering at the
hands of cancer by 2015. To do this, they have had to develop new ways of diagnosing,
imaging and treating it and nanotechnology is at the forefront of this research. The NCI
is focussing on translational research that pinpoints six areas in which nanotechnology
can create the greatest impact:
 The early discovery of cancerous cells and the subsequent creation of molecular
images. This is a key issue as the cancer recovery sequence is radically simplified and
shortened by a quick detection.
 ‘In Vivo’ nanotechnology imaging systems, which provide better molecular insight
than current structures. Also, these models will provide highly reproducible data

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necessary for the treatment of cancer. The new form of imaging will thus in effect
refine, streamline and advance the treatment process.
 Enhanced reporters of treatment effectiveness. This can determine whether a
therapeutic (beneficial) agent is reaching its target and/or killing the cancerous cells
that it is designed to terminate.
 Even devices of such a small size have the capabilities to carry a high load of an anti-
cancer drug, as well as agents that can target a specific area of the body. These
nanoscale agents can also get to those areas that are difficult to access due to any
biological barriers, as well as regions that have been affected by tumours.
 Nanotechnology will greatly advance the current efforts by investigators and
scientists to prevent and control the spread of cancer throughout the body.
Nanoscale devices also prove valuable for delivering cancer vaccines that can engage
the body’s immune system or deliver cancer-preventing nutraceuticals.
 Nanotechnology offers a range of research tools, from chip-based nanolabs capable
of observing and controlling cells, to nanoscale probes that can monitor the
movements of cells, and even individual molecules, as they move about in their
environment. Using these will enable cancer biologists to study, monitor, and alter
any systems that go awry in the cancer process.
As these nanodevices are evaluated in clinical trials, scientists predict that
nanotechnology will serve as a multifunctional tool that will not only be used with
diagnostic and therapeutic means, but will change the very foundations of cancer
diagnosis, treatment, and prevention. The initiation of nanotechnology in cancer
research couldn’t have come at a more appropriate time - the vast knowledge of cancer
genomics and proteomics is providing incredibly important details of how cancer
develops, which, in turn, creates new opportunities to attack the molecular foundations
of cancer. However, scientists currently lack the technological innovations to turn the
positive molecular discoveries into benefits for cancer patients. It is here that
nanotechnology can play a vital role, providing the technological power and tools that
will enable those developing new diagnostics, therapeutics, and preventives to keep up
with today’s expansion of information.
Further research and other studies on the subject suggest that nanotechnology could be
utilized with considerable advantages over currently employed chemopreventive and
chemotherapeutic approaches for cancer. Apart from the nanochemoprevention side of
nanotechnology, studies worldwide have shown that nanotechnology is a plausible
approach for diagnosis, imaging, and therapeutics.
On the basis of discussions with a wide range of clinicians, technologists, and cancer
researchers, it is clear that nanotechnology is now ready to solve these critical problems
in cancer research. While the tests that have been conducted have only currently been
implemented on a small sample of patients, the results have been encouraging. Should

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similar outcomes continue to be repeated, then this new form of cancer treatment can
and will be applied on a much larger scale, which in turn will help the NCI achieve its
main goal of eliminating cancer suffering and death by 2015.
How will these methods improve the treatmentof cancer?
Molecular Imaging and Early Detection:
Nanotechnology can have a huge impact on how clinicians will detect cancer in its
earliest stages. Extremely sensitive devices made of nanoscale components—such as
nanocantilevers (strips of silicon carbide that can detect incredibly small masses),
nanowires, and nanochannels—offer the potential for detecting even the rarest
molecular signals associated with malignant cancer cells.
Detecting such signals for analysis could fall to nanoscale harvesters (which are already
under development), that selectively detach cancer-related molecules such as proteins
and peptides (which are only present in minute amounts) from the bloodstream or
lymphatic system. Investigators have already verified the viability of this approach using
the serum protein albumin (a naturally existing nanoparticle), which collects proteins
that can indicate the presence of cancerous tissue.
Nanotechnology has also been used to create new and greatly improved imaging
techniques to find small tumours. Researchers have shown that incredibly small iron
oxide particles (nanoparticulates) can be used in conjunction with magnetic resonance
imaging (MRI) to accurately identify cancers that have spread to lymph nodes, without
requiring surgery. Furthermore, another area with potential is detecting mutations and
genome volatility. Already, investigators have developed original nanoscale in vitro
techniques that can analyse variations across different tumour types and distinguish
healthy cells from malignant ones. Nanopores are now finding use as DNA sequencers,
and nanotubes are displaying the ability to detect mutations using a scanning electron
microscope.
Additional work could result in a nanoscale system which could be capable of
differentiating among different types of tumours accurately and quickly. This
information would be invaluable to clinicians and researchers. Similarly, investigators
have developed nanoscale systems capable of determining protein expression patterns
directly from tissue. This process uses mass spectroscopy, which measures the unique
atomic mass of the proteins in the tissue and can thus determine its expression pattern.
This technique has shown that it can identify different kinds of cancer and deliver data
that correlates with existing clinical projections.
In addition, nanoscale devices can enable instantaneous monitoring of exposures to
environmental and lifestyle cancer risk factors. This data would be important not only
for identifying people who may be at risk of developing cancer, but also for opening the

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door to more in-depth studies of gene-environment interactions as they relate to the
development of, or resistance to, cancer.
To sum up, nanotechnology will provide the opportunities to develop instruments that
will aid clinicians in detecting cancer early, as well as minimising the potency of
environmental cancer risk factors. This will prove pivotal in advancing cancer treatment,
and ultimately meeting the NCI’s goal of eliminating death and suffering from cancer by
2015.
‘In Vivo’ Imaging:
Currently, one of the most pressing needs in clinical oncology (the study and treatment
of tumours) is the one for imaging agents that can identify tumours that are far smaller
than those detectable with today’s technology. The requirement is to be able to detect
tumours that are a size of 100,000 cells rather than today’s best efforts which can’t
detect tumours smaller than 1,000,000,000 cells. Reaching this level of sensitivity
requires more advanced targeting of imaging agents and generation of a larger imaging
signal. Nanoscale devices are capable of accomplishing both of these necessary
requirements. When attached to a dendrimer (a synthetic polymer with a branched
structure), such as the magnetic resonance imaging (MRI) agent (gadolinium), a
nanoscale device can generate a 50-fold stronger signal than in its usual form. Nanoscale
particles can host multiple gadolinium ions, which affords an opportunity to create a
very powerful contrast agent. This agent would have the potential of meeting the
100,000 cell detection level, which in turn would prove to be a massive breakthrough in
clinical imaging.
First-generation nanoscale imaging contrast agents are already paving the way to new
methods for spotting tumours much earlier in their development, before they are even
visible to the eye. In the future, implantable nanoscale bio-molecular sensors may
eventually enable clinicians to monitor in a more precise manner the disease-free status
of patients who have undergone treatment, as well as individuals susceptible to cancer
because of various risk factors.
Imaging agents will also be targeted to changes that occur in the environment
surrounding a tumour, such as angiogenesis (development of new blood vessels) that
are now beyond our capability to detect in the human body. Already, various
nanoparticles are being targeted to receptors expressed by growing capillaries. Given
that angiogenesis happens in discrete stages and that anti-angiogenic therapies will
need to be tailored for a given angiogenic state, angiogenesis imaging systems that can
differentiate among these stages will be vital for obtaining optimal benefit from healing
agents that target angiogenesis.
Reporters of Efficacy:

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Today, it is the norm for clinicians and patients to wait several months for signs that a
given therapy is working as intended. In too many instances, this delay means that if the
initial therapy should fail, subsequent treatments have a reduced chance of success. The
lag also adversely impacts how new therapies undergo clinical testing. This is because it
leaves agencies reluctant to allow new cancer therapies to be tested on anyone apart
from those patients who have exhausted all other restorative possibilities.
Unfortunately, this set of patients is far less likely to respond to any therapy, especially
to those molecularly targeted therapies that aim to stop cancer early in its progression.
This is an approach that virtually all of scientists’ current knowledge says is the best
approach for treating cancer.
Nanotechnology offers the opportunity for creating extremely sensitive imaging agents
and other diagnostics that can determine whether a therapeutic agent is reaching its
intended target and whether that agent is killing malignant cells or support cells. The
emphasis is obviously to develop systems that can kill the cancerous cells, leaving as
many support cells intact as possible. Targeted nanoscale devices may also enable
surgeons to more easily detect the margins of a tumour before resection (removal) or to
detect micro-metastases in organs or tissues that are distant from the primary tumour.
This information would help to influence therapeutic decisions and have a positive
impact on the patients’ quality-of-life issues.
The greatest potential for immediate results in this area would focus on detecting
apoptosis (programmed cell death) following cancer therapy. Such systems could be
constructed using nanoparticles containing an imaging contrast agent and a targeting
molecule that identifies a biochemical signal seen only when cells undergo the apoptosis
process. Using the molecule ‘Annexin V’ as the targeting ligand (molecule) attached to
nanoscale iron oxide particles, which act as a powerful MRI contrast agent, investigators
have shown that apoptosis can be detected in isolated cells and in tumour-bearing mice
that had undergone successful chemotherapy. Further development of this type of
system could supply clinicians with a way of identifying therapeutic effectiveness in a
matter of just days after treatment.
Other structures could be designed to detect when the p53 system (a tumour-
suppressing protein) is reactivated or when a therapeutic agent switches the
biochemical systemthat it targets in a cancer cell, such as angiogenesis, on or off.
Another possible approach may be to use targeted nanoparticles that would attach
avidly or irreversibly to a tumour and then be released back into the bloodstream in the
form of cells in the tumour undergoing apoptosis following cancer therapy. If these
nanoparticles are labelled with a fluorescent probe, these particles could be easily
identified in a patient’s urine. If they are also labelled with an imaging contrast agent,
such a construct could double as an imaging probe.

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MultifunctionalTherapeutics:
Because of their multifunctional capabilities, nanoscale devices can contain both
targeting agents and curative payloads at levels that can produce high levels of a given
anticancer drug. This is particularly useful in areas of the body that are difficult to
access because of a variety of organic obstructions, including those developed by
tumours. Multifunctional nanoscale systems also offer the prospect of utilising new
approaches to therapy. Examples of these include localised heating or reactive oxygen
generation. Furthermore, combining a diagnostic or imaging agent with a therapeutic in
the same package is another approach being taken to new methods of treatment.
“Smart” nanotherapeutics could in turn provide investigators with the ability to time
the release of an anti-cancer drug or deliver several drugs consecutively in a timed
manner or at multiple locations in the body. Smart nanotherapeutics may also herald
an era of sustained therapy for the cancers that must be treated continually or to
regulate the quality-of-life symptoms that result from cancers that cannot be treated
successfully. This range of “Smart” nanotherapeutics could also be used to contain
engineered cellular “factories” that would create and secrete multiple proteins and
other anti-growth factors that would affect both a tumour and its immediate
environment.
The list of prospective multifunctional nanoscale remedies grows with each new
targeting ligand discovered through the use of tools such as proteomics. Nanoscale
systems containing a given therapeutic agent would be “decorated” with a targeting
agent. This could take the form of a cloned antibody or Fv (fusion protein) fragment to a
tumour surface molecule, or a ligand for a tumour-associated receptor, or another
tumour-specific marker. In most cases, such nanotherapeutics could double as imaging
agents due to their altered appearance.
Many nanoparticles will react to an externally applied field (magnetic, focused heat, or
light) in ways that could make them perfect therapeutics or therapeutic delivery
vehicles. For example, nanoparticulate hydro-gels can be targeted to sites of
angiogenesis, and, once they have bound to those vessels undergoing angiogenesis, it
should be possible to apply localized heat to “melt” the hydro-gel and release an anti-
angiogenic drug. Likewise, iron oxide nanoparticles, which can also serve as the
groundwork for MRI contrast agents, can be heated to temperatures lethal to a cancer
cell merely by increasing the magnetic field at the location where these nanoparticles
are bound to tumour cells.
In some instances, nanoscale particles will target certain tissue strictly because of their
size. Nanoscale dendrimers and iron oxide particles of a specific size will target lymph
nodes without any molecular targeting. Nanoscale particles can also be designed to be

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taken up by cells of the reticuloendothelial system (cells able to ingest bacteria), which
raises the possibility of delivering potent chemotherapeutics to cells or organs that
have been detrimentally affected by tumours.
Nanoscale devices should also find use in creating immuno-protected cellular factories
proficient enough to synthesise and secrete multiple curative compounds. Early-stage
research has already established the value of such cellular factories, and a continued
effort could turn this research into a potent multivalent therapeutic agent capable of
responding to local conditions in a physiologically applicable style.
Prevention and Control:
Numerous developments that nanotechnology will enable in each of the four preceding
advancement areas will also find widespread applicability in efforts to prevent and
control cancer. The advances driven by the National Cancer Institute’s initiatives in study
of proteins and bioinformatics will enable researchers to classify indicators of cancer
susceptibility and precancerous tissue abnormalities.
Nanotechnology will then be used to develop devices able to signal when such markers
appear in the body, and then deliver agents that would reverse any pre-cancerous
changes or kill those cells that have the potential for becoming malignant. Nanoscale
devices may also prove valuable for delivering polyepitope treatment drug that would
engage the body’s immune system. These devices could also be utilised for delivering
cancer-preventing drugs or other chemo-preventive agents in a continued, time-
released and targeted manner.
One exciting proposal for preventing breast cancer comes from work suggesting that
breast malignancies may emanate from a limited population of pluripotent stem cells
(cells that can differentiate into specialised cell types) in breast tissue. Should this prove
correct, it may be possible to develop a nanoscale device that could be injected into the
ductal systemof the breast, bind only to those stem cells, and then deliver an agent
capable of killing those cells. Such an agent could subsequently be distributed to those
women who are at an increased risk of breast cancer, as a preventive therapy.
Research Enablers:
The introduction of nanotechnology into the cancer research environment provides a
vast and varied assortment of tools. A prime example of this is the implementation of
chip-based nanolabs that are capable of monitoring and operating individual cells, as
well as nanoscale probes that can trace the movements of cells as they move about in
their environment. These devices are so sensitive that they can pick up the activities of
individual molecules. The use of such tools will allow cancer biologists to dissect,
observe, and adjust the numerous systems that go askew in the cancer process, and

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identify important genetic and biochemical “choke points” at which the upcoming wave
of molecular therapies may most effectively be directed. Furthermore, nanotechnology
can act as the ideal complement to other technology platforms - the NCI is emphasising
these fields in its investigative initiatives as significant components of the unearthing
and development mechanism that will form the groundwork for both immediate and
long-term advances in cancer prevention, diagnosis and treatment.
The opportunity for nanoscale devices to act as molecular harvesting devices would be a
tool that would prove invaluable to proteomics efforts aimed at identifying tumour-
specific indicators. Similarly, nanoscale agents that can sense the biological alterations
associated with medicinal effectiveness should also find widespread use as a tool for
understanding how cells respond to a variety of modifications. One of the most powerful
short-term uses of nanotechnology to advance basic research will arise from the use of
molecular-sized nanoparticles with a broad range of visual properties, such as quantum
dots to track individual molecules as they move through cells throughout the body. In
tandem with the new generation of mouse models that more exactly replicate the
hereditary, biochemical, and physiological attributes of human cancers, these nanolabels
will prove invaluable for systems-scale research. Augmented focus on the improvement
of nanoscale systems for making concurrent biochemical measurements on multiple
cells, especially those that have been developed in such a way as to mimic tissue
development, will also have a noteworthy impact on fundamental cancer research.
Nanoscale devices may also enable direct analysis of single nucleotide polymorphisms
(SNPs) and large-scale mutational screening for genes that are typically associated with
cancer susceptibility. Real-time analysis should also benefit from a variety of nanoscale
tools and devices. Indeed, nanotechnology should prove to be a valuable technology
platform for the escalating field of cancer molecular treatment research. The devices
that nanoscale research enables the creation, and indeed implementations of, will have
the overall effect of streamlining and increasing the efficiency of the cancer treatment
process.
What problems are associatedwithnanotechnology andhow can they be
addressed?
The use of nanotechnology as a cancer therapeutic has not been without its critics.
Researchers face significant challenges in developing these treatments, and one of these
is making sure that the therapeutics are delivered to the cancerous cells with minimal
damage caused to other body cell. This is made difficult by metastasis (the way in which
cancer cells cause nearby tissue structures to become diseased), and it makes
distinguishing between healthy and malignant cells more tricky. Another difficulty is
overcoming the body’s natural filtration systemin order to get the relevant

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nanoparticles into the patient’s cancer cells. At present, scientists are working on
researching possibilities for the production of a drug to surmount such an obstacle.
While such a drug has not been completed as yet, the rate of research indicates that one
will be available in the near future.
How will nanotechnology continue toimprove cancer treatment inthe
future?
Popular opinion amongst investigators, scientists and clinicians has culminated in a set
of predictions concerning the future prospects of nanotechnology within the field of
treating cancer. Firstly it has been predicted that within the next seven years, techniques
for medical diagnosis and targeted drug delivery (using the methods described above)
could reduce cancer to an easily detectable and treatable illness.
Further developments beyond this date may come in the form of nanorobots. These are
essentially more advanced versions of the multifunctional therapeutics mentioned
earlier. The 70-nanometer wide ‘attack bots’—made with two polymers and a protein
that attaches to the malignant cell's surface—carry a piece of RNA (ribonucleic acid)
called small-interfering RNA (siRNA), which disables the production of a protein, starving
the cancerous cell to death. Once it has delivered its lethal blow, the nanoparticle itself
breaks down into tiny pieces that get eliminated by the body in the urine.
The truly groundbreaking attribute of nanorobots is that you can send in as many of
them soldiers as is required, and they will keep attaching to the dangerous cels, killing
them left, right and centre. This is a far quicker method of stopping the outbreak of
tumours. Additionally, these bots can be modified to preserve other body cells,
improving the efficiency of their tasks. According to Mark Davis, head of the research
team that created the nanobot anti-cancer ‘army’ at the California Institute of
Technology, "the more [nanobots are] put in, the more ends up where they are
supposed to be, in tumour cells." While trials must continue to make sure that there are
no harmful side-effects that have yet to be eradicated, the results have been very
successful thus far, and the prospect of the use of nanobots is a very exciting, and
potentially a landmark one.
Studies from the International Journal of Nanomedicine demonstrated the usefulness of
nanoparticulate technology to enhance the therapeutic effectiveness of other natural
agents used in treating cancer. Based on their study, the concept was very well utilized
by researchers worldwide and, as described above, the outcome of the studies is very
convincing.
What will result as a consequence of such developments?

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The introduction of nanotechnology as a form of cancer treatment will eclipse all current
methods, namely surgery, radiation and chemotherapy. These three processes all
present the risks of tissue damage and incomplete eradication of the cancer. No such
possibility has yet resulted from tests concerning nanotechnological therapeutics.
After the success shown in research of cancer treatments, nanotechnology is already
beginning to make impacts in other areas of chemical engineering. For example,
nanotechnology-mediated delivery of bioactive food components has been shown to be
very effective due to the fact that nanoparticles tend not to pose any toxicity to normal
cells. Further verification of the studies is urgently needed in appropriate animal systems
and in clinical research, but the initial signs are very promising. Moreover, the fact that
these nanoparticles are biodegradable means that they are considered to be ‘safe’.
Considerable investigation is now being devoted to nanoparticle-based delivery of
various drugs to treat a variety of diseases. A number of nanotechnology-based
constructs are currently in clinical or preclinical development, and several of these have
already been approved by the Food and Drug Administration. There are already a variety
of nanocarrier-based drugs on the market today, mostly in the form of nanoparticles or
antibodies. In the near future, the number of therapeutics available will continue to
grow, and the applicability of these will stretch to areas which current drugs cannot
treat. Nanotechnology could be developed as an inexpensive, tolerable, and readily
applicable approach for cancer control and management. In addition, the advancement
in nanochemoprevention might help us to achieve higher concentrations of
phytochemicals (naturally occurring chemicals found in plants) which are inaccessible
when provided as part of a regular diet. It is at present predicted that, on current
progress, a cure for cancer will be available by the year 2015 and it is also anticipated
that nanotechnology will be worth $1 trillion as an industry by that time. A large portion
of the impact will undoubtedly focus on health care and cancer therapy.
While there is some cautiousness that prospective research needs to address the
potential long-term toxicity, degradation, and metabolism of nanotechnology agents
being utilized for integrated imaging, detection, and therapy, the prospects are very
promising for the use of nanotechnology as a therapeutic system. If everything falls into
place at the right time with nanotechnology and its existing and forthcoming
applications for cancer, the NCI can expect very exciting success in the near future.

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