The field of nanomedicine is inherently multidisciplinary requiring the involvement of those with knowledge of engineering, physics, chemistry, biology as well as medicine. The commercialization of nanomedicine adds further complexity and requires additional participation from those with experience in manufacturing, intellectual property, regulatory issues, strategic partnering, and raising investment. Suffice it to say, getting a nanomedicine to the clinic is a tremendous challenge. Given that nanomedicine is still a fairly nascent area, most nanomedicines are currently being developed in academia.
Wyss Institute
The Wyss Institute at Harvard University

Collaborative, Multidisciplinary Efforts

In order to translate these promising therapies and diagnostics to the clinic, it is imperative that the coalescing of this wide range of knowledge from engineering and medicine to manufacturing and intellectual property be allowed to exist even at the early stage … at the academic institution. Due to various reasons and challenges, such pooling together of resources and personnel is not too common in a university setting, but this is changing. The Wyss Institute at Harvard University is one example.

The Wyss Institute

The Wyss Institute at Harvard University is a collaborative effort between researchers, clinicians, corporations, and startups. The Institute is partnership between the following entities:
  • Harvard University
  • Tufts University
  • Boston University
  • Beth Israel Deaconess Medical Center
  • Boston Children’s Hospital
  • Brigham and Women’s Hospital
  • Dana Farber Cancer Institute
  • Massachusetts General Hospital
  • University of Massachusetts Medical School
  • Spaulding Rehabilitation Hospital
To complement the academic and medical expertise provided by these entities, the Wyss Institute also incorporates an Advanced Technology Team and a Business Development Team bringing much-needed project management, commercialization, and industry-related expertise to these partnerships. Two areas of focus of the Wyss Institute that relate to cancer nanomedicine are programmable nanomaterials and implantable vaccines.

Programmable Nanomaterials

Programmable, or smart, nanomaterials can be formed from numerous types of materials including metals, polymers, and ceramics. At the Wyss Institute, nucleic acids (RNA, DNA) are the building blocks of their programmable nanomaterials. Nucleic acid-based nanostructures such as DNA origami are being developed to enable multiplexed diagnostic assays and medical imaging techniques and to form nanoparticle drug carriers targeting diseased sites within the body.
Here’s a video from the Wyss Institute’s website discussing DNA-based programmable nanomaterials.

Implantable Cancer Vaccines

As with other vaccines such as those for the flu, cancer vaccines are medicines that trigger the body’s immune system to fight cancer. Several cancers have been linked to viral (vaginal cancer, cervical cancer, Burkitt lymphoma), bacterial (stomach cancer), and parasitic (bladder cancer) infection. Vaccines against the foreign invaders are being developed, some now approved, to prevent or treat these infection-associated cancers.
The Wyss Institute is developing a vaccine for melanoma using an implantable disk made from a biodegradable polymer which helps draw the patient’s immune cells and redirects those cells to attack the cancer cells … all within the patient’s body. In September 2013, the Wyss Institute initiated a Phase I clinical trial to evaluate their novel, implantable vaccine approach to treat melanoma.

Promising Model - Seed Grants and Industrial Partnerships

To facilitate the launch of new ideas that may transcend into potential medical solutions, the Wyss Institute offers small grants to faculty at Harvard and collaborating academic institutions and medical centers. These grants enable exploratory research that would otherwise be too early-stage for government or industry funding. These early-stage grants are a much-needed source of financing as early-stage funding is extremely challenging to obtain, especially for life sciences efforts.
At the other end of the spectrum of commercialization, complementary to seed grants, the Wyss Institute actively seeks industrial partnerships. These partnerships can help with not only providing additional funding to promising projects, but also in giving insight to researchers regarding market opportunities. The industrial partners are also potential licensees of technologies developed at the Wyss institute, helping to bring the ideas to fruition and eventual commercialization.
 
 
With the continual need to fill their therapeutic pipelines, major biopharma companies are constantly on the lookout to forge key strategic partnerships with smaller biotech companies that have promising alternative therapeutic options in development. A relatively recent trend is the partnering of biopharma companies with nanomedicine startups. As more nanotechnology-related drugs are transitioning from the lab to the clinic, interest in nanomedicine and it’s potential to treat cancer is growing. Some of the major biopharma companies who have recently shown interest in nanomedicine include AstraZeneca, Amgen, Pfizer, Sanofi, and GlaxoSmithKline. Here I will briefly discuss some of the partnerships that these companies have forged.

AstraZeneca

In December 2012, AstraZeneca announced a partnership with Cytimmune to develop multifunctional gold nanoparticles for treating cancer. The gold nanoparticles from Cytimmune are coated to prevent the patient’s immune system interacting with the nanoparticles and can have cancer-targeting agents and cancer therapeutic agents co-attached enabling delivery of the cancer drug to the tumor.
In April 2013, AstraZeneca announced a strategic collaboration with BIND Therapeutics to perform Investigational New Drug (IND)-enabling studies on molecularly targeted kinase inhibitor therapies for cancer. The engineered nanoparticle drug delivery platform developed by BIND has garnered much interest recently from several biopharma companies. BIND’s platform enables preferential accumulation of the desired cancer drug within tumors reducing off-target side effects while delivering more potent amounts of the drug to the tumor for a more efficient cancer-killing effect.

Amgen

In January 2013, Amgen and BIND Therapeutics executed an agreement worth at least $180 million representing one of the first major deals between a large biopharma company and a nanomedicine startup company. Similar to the AstraZeneca deal, Amgen will be using BIND’s nanoparticle platform to target their kinase inhibitor cancer drugs to tumors.

Pfizer

In April 2013, Pfizer announced a $210 million partnership with BIND Therapeutics for development work using the BIND engineered nanoparticle platform to deliver various cancer drugs developed by Pfizer. The companies are working together on preclinical efforts with Pfizer getting exclusive options of which candidate therapies will proceed through clinical trials and commercialization.

Nanotechnology for Cancer - still early but heading in the right direction

These recent deals between major biopharma companies and emerging nanomedicine companies are evidence of the growing interest in nanotechnology for medicine, especially in the area of cancer therapy. Many more developments are ongoing in startup companies and in the academic world. Most cancer nanomedicine developments are still in the preclinical stages although some of these agreements have now helped take promising nanoparticle therapies into clinical trials. With the high cost of taking new therapies through clinical trials, partnerships between the nanomedicine developers and the major biopharma companies are critical and necessary to bring these promising solutions to cancer patients. The fact that these major companies are now investing hundreds of millions of dollars into cancer nanomedicine brings tremendous promise to the field and validation of nanotechnology-based approaches to medicine. Now we must watch and see how the clinical trials pan out.
 
 
Long before gold nanorods, carbon nanotubes, and magnetic nanoparticles were first made in the lab, nanoscale structures made from biological materials were being, and continue to be, constructed in living organisms. Life wouldn’t exist without nanostructures. Proteins that help build our muscles, antibodies that fend off disease and infection, membranes that keep unwanted materials out of our cells, even the fundamental building block of life … DNA, all exist at the nanoscale. What makes nanotechnology for medical applications such a compelling field is the fact that biology already operates at the nanoscale. Why make a diagnostic tool or medical device the size of a cell phone when you can make one the size of a cell membrane?
Considering life naturally works on the nanoscale, much research is now underway to engineer nanostructures out of biological materials. Today I’ll discuss DNA.

DNA and Nanotechnology

Deoxyribonucleic acid, or DNA, is a relatively simple molecule structurally speaking. It is primarily made up of only four different building blocks - the DNA alphabet of the bases adenosine (A), guanine (G), thymine (T), and cytosine (C). The structure of DNA that people are most familiar with is the double helix where the bases A, G, T, and C form a twisted ladder. However, using these same four bases, one can construct almost any shape that is desired. The question, though, is … why build anything using DNA?

Why Use DNA to Build Nanostructures?

DNA is a robust and biologically compatible material that is relatively easy to put together. DNA can last for thousands of years, even has been extracted from fossils. It has been estimated that DNA has a half-life of over 500 years, meaning that after 500 years, half of the DNA in a sample remains intact. Using DNA synthesizer equipment, long strands of DNA can be readily assembled by sequentially attaching each base (A, G, T, C) forming a chain … like putting beads together on a string. Multiple copies of the synthesized DNA can then be cloned within living organisms, typically bacterial or yeast cells. In fact, many companies now exist that provide DNA synthesis as a service. For shorter strands of DNA and more complex molecular architectures, such as those used to create nanostructures, standard DNA amplification and replication techniques can be used. Most often, DNA nanostructures are made using widely-available polymerase chain reaction (PCR) machines or thermocyclers.

Types of Nanostructures from DNA

Some of the earliest structures made from DNA that were not used for genetic purposes were aptamers. Aptamers are sequences of nucleotides (DNA, RNA) or peptides that are constructed to have a high affinity for a desired target molecule. DNA aptamers have been made for targeting platelet-derived growth factor (PDGF) for treating age-related macular degeneration, for binding thrombin to maintain anticoagulation during heart bypass surgeries, and for attaching to nucleolin for treating acute myeloid leukemia (AML). Many aptamers are now undergoing clinical trials for a variety of therapeutic purposes.
While aptamers were first discovered in 1990, other, more complex DNA structures have been, and continue to be, developed. These include DNA origami and DNA nanotrains. In fact, DNA nanotechnology has been around since the 1980s with attempts to create non-biological applications of DNA such as computing. It are these architectures that most would consider being DNA nanostructures due to their complexity and multifunctionality.

DNA Origami, Nanotrains, and Cancer Nanomedicine

DNA Origami
Researchers have been able to construct all sorts of shapes using DNA … spheres, boxes, scissors. One area in nanomedicine where DNA origami and DNA nanotrains are showing potential is in drug delivery. By folding DNA into tubes or boxes that can be opened and closed, researchers have been able to load drugs into these nano-assemblies. The drug remains contained with the DNA vessel until the infected or diseased cells are reached. Once inside the cells, the DNA constructs break open and release the drug within its intended cellular targeted minimizing the potential for the drug to cause unwanted side effects and possibly reducing the amount of drug required. Feasibility studies have been performed on leukemia and lymphoma cells as well as breast cancer cells for delivery of doxorubicin.
Aside from DNA aptamers, several of which are in clinical trials, the clinical benefits of more complex DNA nanostructures are still to be proven. However, the versatility, biocompatibility, and robustness of DNA are features that could prove DNA to be a compelling alternative to non-biological nanomaterials such as metals and synthetic polymers. For more information on DNA origami see the downloadable PDF from Nature.
DNA origami
Click on image above to download PDF on DNA origami from the journal, Nature.
 
 
One of the most unique nanomaterials is the carbon nanotube, a hollow structure made of carbon atoms linked together and rolled up like chicken wire. Carbon nanotubes, or CNTs, have an amazing set of properties. They are the strongest known materials by weight (100 times stronger than steel). Through different processing techniques, CNTs can have high electrical conductivity or can be semi-conductive, generating interest with computer chip manufacturers. CNTs also have unique optical properties. They absorb almost any form of light from far-ultraviolet to far-infrared. They exhibit photoluminescence, meaning they emit a different wavelength of light back from the light to which they are exposed. CNTs also have unique spectroscopic signatures enabling them to be readily identified. Due to their versatility, CNTs have found themselves in a variety of products and applications including bicycles, displays, sensors, and solar cells.
Kohlenstoffnanoroehre Animation
Not surprisingly, CNTs are also being used in a variety of potential medical applications. One that I will discuss today is x-ray imaging, the fundamental technique used in computed tomography (CT) scans and mammograms.

The Beginning of X-Ray Imaging

X-rays were discovered by Wilhelm Conrad Roentgen in 1895. The field of medical imaging was quite new but rapidly grew following the invention of the x-ray tube by William Coolidge in 1913. Coolidge was a researcher at General Electric (GE) at the time and here’s a copy of his patent. The design of this first x-ray tube, or Coolidge tube as it came to be known, contained tungsten filaments and forms the basis of most x-ray sources used in medical imaging today.
Fixed anode x-ray tube

Limitations of Current X-Ray Sources

X-ray tubes work by resistively heating the metal filament contained within the tube up to 1000 degrees Celsius resulting in emission of electrons from the filament, typically tungsten. The emitted electrons collide with a metal target (tungsten, molybdenum, copper) within the tube generating x-rays. Unfortunately, this process of producing x-rays is very inefficient. A lot of power is required to heat the filament to generate electrons. Many CT scanning systems require well over 100 kilowatts of power. That’s equivalent of over 100 kitchen microwave ovens running at the same time. Just imagine the electric bill. Compounding the issue, only about 1% of the energy used is converted to x-rays, the remaining 99% just generates heat … a lot of it. In fact, CT scanners require their own chillers to keep the machines cool.

Why Use Carbon Nanotubes as X-Ray Sources?

When filaments are used to generate x-rays, this is called thermionic emission. A large amount of heat is needed to generate flow of charged particles such as electrons. In contrast, carbon nanotubes are field emitters and can generate electrons at room temperature. Essentially, the electrons are projected from the tip or end of the nanotube. Less power is required and less heat is generated when using field emitters. With less heat and less power, portable but powerful x-ray machines could be realized. However, due to manufacturing challenges and high vacuum requirements, field emission devices have had limited commercial success.

Current Status of Carbon Nanotubes for X-Rays

Despite the challenges of bringing field emitting devices to market, the use of carbon nanotube field emitters for x-ray imaging has made tremendous progress. XinRay Systems, in collaboration with the National Cancer Institute, initiated an observational clinical trial for breast cancer in January 2013 at the University of North Carolina Lineberger Comprehensive Cancer Center. The trial will compare XinRay’s carbon nanotube x-ray imaging device with conventional mammograms. This study is estimated to be completed by January 2015.
 
 
Many types of materials are being used in the development of nanomedicines and advancements continue to be made in the methods used to fabricate nanoscale objects. These fabrication methods are enabling the scaling down of structures, devices, and systems using almost any material. The common classes of materials used in nanomedicine are:
  • silicon
  • carbon
  • biological
Today, I’ll focus on metals, ceramics, and polymers.

Metals, Nanotechnology, and Medicine

Metals have been used in medicine for a long time. Most medical applications using metals have used the structural qualities of metals such as plates and screws for fixating bone after fracturing, expandable mesh for stents to keep arteries open, and casings for implantable devices such as pacemakers and defibrillators. Now, with the ability to forge nanoscale structures out of metal, a wider range of medical applications are being realized.
Here are some examples of metal nanomaterials and their medical uses:

Ceramic Nanomaterials

The term ceramic encompasses a wide range of materials including metal oxides such as alumina (aluminum oxide) and titanates (titanium oxides) and non-oxides such as carbides (silicon carbide, tungsten carbide) and nitrides (boron nitride, aluminum nitride). Ceramics are typically thought of as hard but brittle materials. While this is generally the case for bulk materials, when ceramics are used in nanostructures, rather unique properties can be realized. For example, ceramics at the nanoscale can be used as electrical insulators, conductors, or exhibit piezoelectricity and possess a wide range of optical properties.
Here are some examples of ceramic nanomaterials and their medical uses:

Polymers and Nanomedicine - A Diverse Class of Materials

Polymers are synthetic organic materials that can be formed into almost any shape and can be tailored with almost any property. Polymers can be strong (Kevlar), flexible (rubber), waterproof (Gore-Tex), water-loving (hydrogels), transparent (acrylics), conducting (polypyrrole, polythiophene), insulating (Kapton), piezoelectric (PVDF), even magnetic … the list goes on. Another advantage of polymers is that many materials made from polymers are biocompatible or can be made biocompatible. In fact, many of the materials in our bodies, such as DNA, RNA, various sugars, and many proteins are all polymers. These are typically referred to as biopolymers (polymers made by living organisms). The shear versatility of polymeric materials combined with precise nanofabrication techniques shows tremendous promise for the future of nanomedicine.
ADN animation
Here are just a few examples of how polymeric nanomaterials are being developed for medical uses:
 
 
Sandia
Sandia National Laboratory Center for Integrated Nanotechnologies
The United States Department of Energy runs a total of 17 National Laboratories spread throughout the U.S. These labs possess some of the most advanced equipment and technologies in the world and are populated with teams of scientists and engineers working on some of the most challenging technical projects. Being under the operation of the Department of Energy, one would expect that the focus of these labs is energy. These labs are working on much more than this. Here is a map from Wikipedia of the 17 labs here in the U.S.
US DOE National Labs

The National Labs and Medicine

The National Labs operated by the U.S. Department of Energy have led, or participated in, many major medical-related projects including the Human Genome Project and the Artificial Retina Project. Both of these projects were successful, but took many years and multiple institutions to complete. The Human Genome Project required worldwide participation and resulted in the mapping of all the genes in human DNA laying the foundation for further insight into many diseases. The Artificial Retina Project took over $100 million dollars to complete and resulted in the world’s first bionic eye for the blind. Due to the foundation laid by the Artificial Retina Project, in February 2013, the FDA approved the Argus II, a retinal prosthesis that gets implanted into the back of the eye to aid retinitis pigmentosa patients see light.
The seven National Labs that have significant programs involving nanotechnology and medicine are:
  • Argonne National Laboratory near Chicago, Illinois
  • Los Alamos National Laboratory in Los Alamos, New Mexico
  • Sandia National Laboratory in Albuquerque, New Mexico
  • Pacific Northwest National Laboratory in Richland, Washington
  • Oak Ridge National Laboratory in Oak Ridge, Tennessee
  • Lawrence Berkeley National Laboratory in Berkeley, California
  • Brookhaven National Laboratory on Long Island in New York
I will highlight four of these labs today: Argonne, Los Alamos, Sandia, and Pacific Northwest.

Argonne National Laboratory (ANL)

Argonne
Argonne National Laboratory Center for Nanoscale Materials
The Center for Nanoscale Materials (CNM) at Argonne has fabrication, processing, and characterization capabilities that enable the development of novel materials that take advantage of the unique properties of materials that occur at the nanoscale. As with many of the National Labs, the facilities at CNM are typically available for use by not only the lab employees but also researchers from academia, industry, and other government agencies. This allows access to cutting edge technologies that would be otherwise unattainable for most researchers.

Of particular relevance to cancer nanomedicine, researchers at Argonne are using titanium dioxide nanoparticles and magnetic nanomaterials to target and kill cancer cells. Here’s a video from ANL discussing these projects.

Los Alamos and Sandia National Laboratories (LANL, SNL)

Los Alamos
Los Alamos Gateway Facility
The Center for Integrated Nanotechnologies (CINT) is a joint operation between Los Alamos and Sandia National Laboratories. As the name suggests, CINT not only has facilities for making and analyzing nanostructured materials, but also provides the capability to integrate such materials into devices. Optical, biological, and composite nanomaterials are all being developed at CINT along with methods to integrate these nanomaterials into microfluidic devices for lab-on-a-chip applications.

Pacific Northwest National Laboratory (PNNL)

Picture
PNNL Environmental Molecular Sciences Laboratory
Of particular importance to nanomedicine is the investigation of potential toxicities that may be associated with the use of nanomaterials for medical applications. Researchers at PNNL are addressing the concerns of nanotechnology and toxicity, a term that has become known as nanotoxicology. PNNL facilities have the capability to assess potential nanotoxicity across all levels of biology from cells to tissue to organs using a combination of pathology, pharmacokinetics, genomics, and proteomics.

The unique properties of materials at the nanoscale not only open up novel applications, but also may present novel challenges regarding potential toxicity. This is an evolving area of research shrouded in much controversy with involvement from many government, academic, and industry institutions across the globe. Nanotoxicity is a topic that will be discussed in future posts … likely more than once.
 
 
Before a drug or device can be used to treat disease, clinical trials are needed to prove that the therapy is safe, yet effective. These clinical trials can take many years and millions of dollars to complete and a favorable outcome is not guaranteed. In fact, only 5% of cancer drugs that enter into clinical trials end up successfully achieving approval for use. That means for every cancer drug that gets approved, 19 others have failed. In comparison, 20% of cardiovascular drugs successfully complete clinical trials.

Why Such a High Rate of Failure for New Cancer Drugs?

The reasons for the high rate of failure for new cancer drugs are many, but here are a few, mostly stemming from the fact that cancer is a very complex and ever-evolving disease:
  • Each patient’s cancer is different. The cancer’s response to therapy can vary patient-to-patient.
  • Cancer can gain resistance to many therapies, so over the course of a clinical study, the overall effectiveness of the therapy being studied can diminish. Metrics such as Progression-Free Survival (PFS), Disease-Free Survival (DFS), and Relapse-Free Survival (RFS) are all used to evaluate the success of a drug going through clinical trials.
  • Preclinical models for cancer used in the lab to assess the potential toxicity and effectiveness of the therapy prior to clinical trials are not reliable predictors of the actual human disease. What may look promising in the lab doesn’t always translate to success when put through clinical trials.

What is Being Done to Improve New Cancer Drug Success?

All is not doom-and-gloom for cancer drug development. Many approaches are being made to improve the success rates of new cancer drugs going through clinical trials. These approaches include the use of adaptive clinical trials which allow for changes to occur during the clinical trial based on interim results, more targeted therapies specific to the cancer being treated, and tumor profiling to hone in on the patient population that is predicted to be best suited for the therapy being tested.

Who Pays for Clinical Trials?

Clinical trials for new drugs take a lot of time (average of 8 years for cancer drugs) and hundreds of millions of dollars to complete, with cancer clinical trials being some of the most expensive studies to perform. So, who pays for these trials? Clinical trials are paid for, or sponsored by, non-profit foundations, biotechnology and pharmaceutical companies, government agencies, and medical institutions. In addition to the hundreds of biotechnology and pharmaceutical companies that are developing new cancer drugs, some of the major sponsors of cancer clinical trials include:

Who Performs Clinical Trials?

Clinical trials are performed at various types of medical institutions including clinics, community hospitals, cancer centers, veteran's hospitals, academic medical centers, and doctor’s offices. Typically, the type of therapy being tested, the complexity of the study, and the desired patient population will dictate where the clinical trial will take place. One of the most comprehensive resources for finding clinical trials for cancer is the National Cancer Institute’s Clinical Trials database, where you can search for trials by cancer type and location.

How to Find Out More About Clinical Trials?

 
 
As with any other therapy, before cancer nanomedicines can be used in patients, they will need to tested for safety and effectiveness through controlled, clinical trials. While numerous nanomedicines are still in the early stages of development, there are several now in clinical trials for cancer. I’ll introduce three of these here today.

Calando Pharmaceuticals

Calando Pharmaceuticals, is developing a nanoparticle-based method to deliver small interfering RNA (siRNA) to cancer cells. Calando recently completed patient enrollment in a Phase 1b clinical trial targeting a variety of solid tumor cancers. Enrollment in the trial was completed in August 2012, see here for press release. At the time of this post, data from that trial was still being analyzed. Treating cancer with siRNA is a very promising approach but has been hindered by the challenge of getting the siRNA into the cancer cells. Calando’s approach has the potential to overcome this hurdle by:
  1. packaging the siRNA to protect it from being broken down by the body before reaching the cancer cells, and
  2. preferentially targeting the cancer cells delivering more of the siRNA to its intended destination.

Cerulean Pharma

Cerulean is conducting clinical trials of a nanopharmaceutical formulation of camptothecin, a powerful chemotherapy. Original formulations of camptothecin were unable to be tolerated by most patients, therefore less potent forms of the chemotherapy were developed and are now in use for various cancers. Cerulean is developing a novel, nanoscale form of camptothecin, currently being called CRLX101, that should provide similar, highly potent anti-cancer effects as the original formulation but in a more tolerable form for patients. This is accomplished by taking advantage of the fact that the blood vessels around tumors have larger pores than those around healthy tissue. The Celurean formulation of camptothecin is small enough to penetrate through the larger pores of blood vessels near the tumor but too large to move through the pores of blood vessels near healthy tissue. As a result, the chemotherapy preferentially accumulates in the tumor where it needs to be and less of the drug ends up where it shouldn’t (anywhere else but the tumor), reducing the possibility of harsh side effects to the patient.

BIND Biosciences

BIND Biosciences is developing polymer nanoparticles that can carry, target, and release therapies to cancer cells. Their lead compound, BIND-014, is a cancer-targeting, polymer nanoparticle containing docetaxel, a well-proven chemotherapy, and has just entered (March 2013) into two Phase 2 clinical trials: one for metastatic prostate cancer and one for non-small cell lung cancer. Packaging the chemotherapy in the polymer nanoparticle keeps the drug at bay until the tumor is reached. Targeting molecules on the surface of the polymer nanoparticles attach to cancer cells helping drive the nanoparticles and the drug payload to the tumor. Once at the tumor site, the chemotherapy is then released over time for optimal effect. Completion of both of these trials is estimated to be December 2015. Note that if these Phase 2 trials are successful and BIND-014 moves to the final, Phase 3 trial, there will still be several more years after completion of Phase 2 before this promising platform gets approval.
 
 
The National Cancer Institute (NCI) was established in 1937 and is one of the 27 National Institutes of Health (NIH) in the United States. NCI is focused on cancer research including the diagnosis, treatment, and prevention of the disease as well as determining what causes cancer. With an average annual budget of approximately $5 billion, NCI is one of the most active funders of cancer nanomedicine.

Relevant Programs at NCI

Many nanotechnology programs at NCI are established through the NCI Alliance for Nanotechnology in Cancer. Current programs through the Alliance include:
Check here for a list of past program awardees.

Research Funding of Nanomedicine at NCI

Through the above-mentioned programs and other funding mechanisms, NCI introduces numerous opportunities throughout the year for researchers to propose projects and programs for funding. Many topics are sought including:
  • Cancer prevention and risk
  • Tumor development
  • Disease recurrence
  • Detection
  • Diagnosis
  • Prognosis
  • Treatment and outcomes
  • Molecular analysis
  • Emerging technologies
  • Imaging technologies
  • Bioengineering
  • Image-guided interventions
Check here for a list of current funding opportunities at NCI for nanotechnology.

For More Information

  • Visit the NCI website for more information on nanotechnology at NCI 
 
 
The potential of nanotechnology to impact how we diagnose, treat, and monitor cancer is far reaching. I have mentioned applications such as drug discovery and drug delivery. Today, I will provide examples of nanotechnology being applied to diagnostics, imaging, and therapy for cancer.

Nanotechnology and Cancer Diagnostics

With many new therapies for cancer under development, there is still a desire to catch the disease as early as possible; doing so enables the use of less harsh forms of treatment such as less aggressive surgery and lower doses of chemotherapy. One way to achieve early detection of cancer is to look for molecules within the body that indicate the presence of a tumor. These molecules are called biomarkers. Much work is being done on developing techniques to use blood, urine, or saliva rather than tissue samples to diagnose and monitor cancer. Using body fluids instead of biospies (tissue samples) provides for non-invasive methods to monitor disease. The challenge with detecting cancer biomarkers in body fluids is the fact that the biomarkers for the disease are typically in such low quantities that standard analytical techniques cannot measure the presence of the biomarkers. A variety of methods using nanoparticles are being developed that can either concentrate the biomarkers to a level where they can be detected or produce a signal that can be amplified and measured. One such method that is being investigated for early detection uses iron oxide nanoparticles combined with mass spectrometry to measure the presence of cancer biomarkers in urine.

Nanotechnology and Medical Imaging for Cancer

There are numerous methods used for medical imaging. These techniques include:
Check here for more information on currently-used medical imaging techniques.
The use of nanoparticles is being investigated to enhance all of these existing imaging methods and to enable new methods such as near infrared and Raman imaging. One example is being developed by Endomagnetics, Ltd. where magnetic nanoparticles are being used in conjunction with a handheld magnetic sensing device to determine whether cancer has spread to the lymph nodes. If cancer is detected in the lymph nodes, then the disease may have spread to other parts of the body requiring further investigation and potentially more aggressive treatment. The lymph node closest to the tumor, the sentinel lymph node, is the first to be analyzed. If no cancer is detected, then no further investigation is needed. To find the sentinel lymph node, a tracer molecule, typical a radioactive material, is injected into the tumor and then imaged to find the node. Once the sentinel lymph node is found, a biopsy of the node is taken and analyzed for cancer. By using magnetic nanoparticles for tracing, radioactive materials are not needed eliminating health problems typically associated with radioactivity and increasing the number of facilities that can perform the procedure (there are stringent requirements for handling radioactive materials).

Nanotechnology and Cancer Therapy

I mentioned the albumin-based nanoparticle therapy, Abraxane, in a previous post. While this approach has given metastatic breast cancer patients a less toxic way of treating their cancer, therapeutic methods that take advantage of the unique properties of nanomaterials and of the ability to create complex nanostructures is where nanomedicine can make a revolutionary impact. For instance, an emerging area of interest is in the use of nanoparticles to deliver lethal heat to cancer cells or to thermally enhance the delivery of cancer drugs. While thermal therapies such as hyperthermia have long been attempted to treat cancer, they have had a history of being rather ineffective, especially when used alone. Furthermore, side effects such as burns, blisters, pain, and fatigue have limited adoption of hyperthermia.
Developments are now underway using nanoparticles that rapidly heat up when exposed to some form of electromagnetic energy such as near infrared (NIR) light or radio frequency (RF) waves to enable thermal treatment of cancer. The use of nanoparticles helps to localize the heat to only those areas where the nanoparticles reside and where the electromagnetic energy is directed. The nanoparticles are small enough to enter and accumulate within the tumor and even within the cancer cells themselves. Several companies are using the unique absorption and thermal properties of nanoparticles to treat cancer including MagForce AG, Nanospectra Biosciences, Actium Biosystems, and Medical Nanotechnologies (disclaimer: I am a co-founder of Medical Nanotechnologies).