Fighting cancer using nanotechnology

Nanotechnology in Cancer Research

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This time-lapse image shows the trajectories of NIH H1650 tumor cells (green)
moving through a blood sample.
Credit: R. J. Wilson, Ph.D.; C. M. Earhart, Ph.D.; and S. X. Wang, Ph.D.

Nanotechnology is the application of materials, functionalized structures, devices, or

systems at the atomic, molecular, or macromolecular scales. At these length scales,
approximately the 1-100 nanometer range as defined by the U.S. National
Nanotechnology Initiative (NNI), unique and specific physical properties of matter
exist, which can be readily manipulated for a desired application or effect.
Furthermore, nanoscale structures can be used as individual entities or integrated
into larger material components, systems, and architectures. Nanotechnology-based
structures and devices are already enabling a large number of novel applications in
various fields – including medicine.

Clinical Use
The earliest nanotechnology-enabled imaging agents and cancer drugs were
approved by the U.S. Food and Drug Administration (FDA) over a decade ago, and
FDA approved nanomedicines include iron oxide nanoparticles for enhanced MRI
imaging contrast and Abraxane®, a nanoparticle formed by binding the serum
protein albumin to the chemotherapy drug paclitaxel, and Doxil®, a pegylated
liposomal formulation of the chemotherapy drug docetaxel. Abraxane improves
patient tolerance of the drug paclitaxel by stabilizing the drug for in vivo delivery
without requiring the use of non-biocompatible chemical stabilizers. For some
patients and cancers, Doxil improves the therapeutic efficacy of docetaxel and
reduces cardiomyopathy, a dangerous side effect of the drug.
A number of nanomedicines and nanoparticle drugs have received Investigational
New Drug (IND) approval from the FDA are currently undergoing clinical trials.
Although some are intended to improve performance of existing chemotherapy
drugs, as with Abraxane and Doxil, others enable use of potent compounds that are
too toxic or insufficiently biocompatible for use without the pharmacokinetic
advantages conferred by the nanoparticle packaging. Nanoparticles are also being
investigated for delivery of nucleic acids and proteins that are unstable in blood,
such as small interfering RNA (siRNA) for RNA interference (RNAi) therapy, and
molecularly targeted therapies such as tyrosine kinase inhibitors.

Treatment and Therapy

Research on nanotechnology cancer therapy extends beyond drug delivery into the
creation of new therapeutics available only through use of nanomaterial properties.
Although small compared to cells, nanoparticles are large enough to encapsulate
many small molecule compounds, which can be of multiple types. At the same time,
the relatively large surface area of nanoparticle can be functionalized with ligands,
including small molecules, DNA or RNA strands, peptides, aptamers or antibodies.
These ligands can be used for therapeutic effect or to direct nanoparticle fate in vivo.
These properties enable combination drug delivery, multi-modality treatment and
combined therapeutic and diagnostic, known as “theranostic,” action. The physical
properties of nanoparticles, such as energy absorption and re-radiation, can also be
used to disrupt diseased tissue, as in laser ablation and hyperthermia applications.
Integrated development of innovative nanoparticle packages and active
pharmaceutical ingredients will also enable exploration of a wider repertoire of
active ingredients, no longer confined to those with acceptable pharmokinetic or
biocompatibility behavior. In addition, immunogenic cargo and surface coatings are
being investigated as both adjuvants to nanoparticle-mediated and traditional
radio- and chemotherapy and as stand-alone therapies. Innovative strategies
include the design of nanoparticles as artificial antigen presenting cells and in
vivo depots of immunostimulatory factors that exploit nanostructured architecture
for sustained anti-tumor activity.

Early Detection and Diagnosis

Although not yet deployed clinically for cancer detection or diagnosis, nanoparticles
are already on the market in numerous medical screens and tests, with the most
widespread use that of gold nanoparticles in home pregnancy tests. Nanoparticles
are also at the heart of the Verigene® system from Nanosphere and the T2MR
system from T2 Biosystems, currently used in hospitals for a variety of indications.

For cancer, nanodevices are being investigated for the capture of blood borne
biomarkers, including cancer-associated proteins circulating tumor cells, circulating
tumor DNA, and tumor-shed exosomes. Nano-enabled sensors are capable of high
sensitivity, specificity and multiplexed measurements. Next generation devices
couple capture with genetic analysis to further elucidate a patient’s cancer and
potential treatments and disease course.

Already clinically established as contrast agents for anatomical structure,

nanoparticles are being developed to act as molecular imaging agents, reporting on
the presence of cancer-relevant genetic mutations or the functional characteristics
of tumor cells. This information can be used to choose a treatment course or alter a
therapeutic plan. Bioactivatable nanoparticles that change properties in response to
factors or processes within the body act as dynamic reporters of in vivo states and
can provide both spatial and temporal information on disease progression and
therapeutic response.

Research Tools
Nanotechnology can also be used for development of research tools to advance the
study of cancer. Examples include in vitro tumor models, such as vessel perfused
microfluidic chips that mimic tumor microenvironment and enable study of
transport properties within tumors and devices that use nanoparticle probes to
study cellular drug responses and mechanisms.

Benefits of Nanotechnology for Cancer

Nanotechnology offers many possible benefits to cancer therapy, detection and
diagnosis. The benefits begin by way of the fundamental properties of
nanotechnology and the biological challenges of which it can help to overcome.
Nanotechnology in Cancer
Treatment
Nanotechnology cancer treatments may lead to destroying cancer tumors with
minimal damage to healthy tissue and organs, as well as the detection and
elimination of cancer cells before they form tumors.
Most efforts to improve cancer treatment through nanotechnology are at the
research or development stage. However there are many universities and
companies around the world working in this area.
The next section provides examples of the research underway, a few of the
methods discussed have reached the pre-clinical or clinical trial stage.

Nanotechnology Cancer Treatments; Nanoparticle Chemotherapy

A targeted chemotherapy treatment under development uses a nanoparticle
called CRLX101. The company developing this targeted chemotherapy method
is called Cerulean Pharma.
Researchers at the University of Georgia are working on a method to fight
prostate cancer. They are using nanoparticles to deliver a molecule called IPA-
3 to the cancer cells. In laboratory mice studies the IPA-3 appears to reduce
the growth of prostate cancer cells.
Researchers are testing the use of chemotherapy drugs attached to
nanodiamonds to treat brain tumors. The nanodiamond/chemotherapy drug
combination stays in the tumor longer than the chemotherapy drug by itself,
which should increase the effectiveness.
For more see Nanoparticle Chemotherapy

Nanotechnology Cancer Treatments; Heat

Another technique being developed works on destroying cancer tumors by
applying heat. Nanoparticles called AuroShells absorb infrared light from a
laser, turning the light into heat. The company developing this technique is
called Nanospectra.
Targeted heat therapy is being developed to destroy breast cancer tumors. In
this method antibodies that are strongly attracted to proteins produced in one
type of breast cancer cell are attached to nanotubes, causing the nanotubes to
accumulate at the tumor. Infrared light from a laser is absorbed by the
nanotubes and produces heat that incinerates the tumor.
Another method that targets individual cancer cells inserts gold nanoparticles
into the cells, then shines a laser on the nanoparticles. The heat explodes the
cancer cells.
We all know how tough a cancer treatment can be. Traditional cancer treatments such as
surgery, radiation and chemotherapy do not only harm the cancer cells, but often also healthy
ones. The treatments therefore often lead to unwanted side effects such as nausea, vomiting,
hair loss and infection. And yet, there is no guarantee for a cure.

A powerful weapon
One of the ideas behind nanotechnology in cancer treatment is in many ways simple. Basically, it
tries to target the effect of anti-cancer drugs more precisely. More accurately targeted treatment
prevents us from harming healthy cells.
One of the methods, that has been tested on mice, is to inject a particular type of nanoparticle
directly into the cancerous tumour. After the injection, a laser heats up the nanoparticles which
then damage or even kill the cancer cells.

Early diagnosis is key

Yet another use of nanotechnology in the fight against cancer aims to locate the tumour at an
earlier stage than would otherwise have been possible. Nanoparticles designed to attach to the
cancer cells make tumours visible in scans earlier in the development of the disease. Since early
diagnosis is vital for curing cancer, this is an important step in the fight against the disease.

The science of extremely small

things
Nanotechnology is about manipulating matter at extremely small
sizes. We do that because we are then able to change how some
substances behave. Gold for instance, will change its colour and
become red when it is broken down to the nano scale. That red
colour has been used for centuries to give red stained glass its
colour. Nanoparticles are, in other words, not something new, they
also exist in nature. But, nanotechnology makes it possible to
engineer nanomaterials and make use of their special properties.