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A targeted approach to cancer treatment: Part II, Nanotechnology

12 Aug 15 - 12:00AM Skills Alliance  | Carl Marotta blog


By Carl Marotta
CEO Skills Alliance


Given all of the recent developments in the world of cancer treatment, I decided to write a series of small blogs focused around the work Skills Alliance has been supporting across our pharmaceutical client base. Initially, this was personal research to better understand the work we were supporting but I felt this might also be interesting to others hence the blog.

This blog outlines how cancer treatment is being revolutionised via the development of nanotechnology and how this technology can assist with both early diagnosis and treatment.

The best place to start would be to briefly explain nanotechnology. Put very simply, Nanotechnology is science, engineering, and technology conducted at the nanoscale, which is about 1 to 100 nanometers. One nanometer is extremely small, to be specific it is a billionth of a meter and it was first discussed by a physicist, Richard Feynman at an American Physical Society meeting at the California Institute of Technology (CalTech) on December 29, 1959.1 Richard Feynman led a talk the manipulation of atoms and molecules which was titled ‘There’s Plenty of Space at the Bottom’2 but it was not until many years later that this would become reality as we could visible see these atoms. Following the development of the scanning tunneling microscope (STM) and the atomic force microscope (AFM) in the 1980’s, nanotechnology then became a reality. This technology is now being manipulated across sectors, not only for the healthcare industry, but for energy and electronic applications. The image below gives you an idea of size in comparison to a tennis ball.3


 
Present Time

If we now fast forward 2015 and focus on the scientific application of this technology in cancer treatment it becomes very exciting. This technology is being developed to destroy cancer cells with very little damage to healthy cells and to also detect cells very early on so that we can then remove the cells before they form tumours. The National Cancer Institute formed an Alliance for Nanotechnology in Cancer with a focus on research in this field.3 This alliance is focused on helping support research into the application of this technology in the fight against cancer.

Nanotechnology can be used to support early diagnosis resulting in increased survival rates as well as treatment for already formed tumours. Below is a brief explanation of how each works.

Early Diagnosis

This is a vital part of the fight against cancer and nanotechnology assists with this in both the imaging and screening of cancerous cells. Nanotechnology can provide new contrast agents and materials to allow for earlier and more accurate screening and detection. If we are able to see the cancerous cells before they turn into tumour or even in the precancerous stage and eliminate them, this would be a huge lifesaving tool. One example of this could be in colorectal cancer detection where early detection is very important. The Centre of Cancer Nanotechnology Excellence at Stanford University developed a technique using gold nanoparticles to seek out and bind to cancer cells which can then be viewed via an endoscope and removed.9

Treatment

The way in which nanotechnology contributes to the treatment of cancer is again still being developed but several companies are now in late stage trials or have compounds on the market. They have done this by developing nanocarriers or more simply put, delivery systems to target specific cancer cells. Current treatment via chemotherapy causes damage to healthy cells as well, which is associated with the side-effects observed after chemotherapy treatment and a complete cure is not always achieved. Nanotechnology allows for a targeted approach to treatment with only the cancerous cells being targeted by the chemotherapy drug of choice. By using these nanocarriers, you can reduce the risk to the patient, reduce the breakdown of the drug before it targets the cells and increase the absorption into the cancerous cells.4

The cancer cells are targeted in two main ways currently, by passive or active targeting.

Passive targeting is focused on enhanced permeability and retention which basically means, due to the size and surface properties of nanoparticles, they can permeate into cancer cells that tend to have leaky blood vessels and poor lymphatic draining resulting in an accumulation on the particles. Mauro Ferrari, a professor of nanotechnology at the University of Texas Health Science Centre, the M.D. Anderson Cancer Centre, and Rice University in Houston, USA has been conducting research into this area and is quoted as saying. “The size, shape, physical properties, density and charge all affect how particles travel through the body, and whether or not they will cross biological membranes." 6 His work is an example of biological barriers such as the vascular wall dominating the distribution of injected nanoparticles in the body.

Active targeting is exactly as it sounds, nanoparticles that will actively target and attach to cancerous cells due to the molecules expressed on their cell surface. This process was developed as the 2nd generation of active nanovectors and is a much more targeted approach reducing risk and side effects as discussed. Receptor cell binding is used in this instance and allows the molecules on the surface of the nanoparticle to actively target and deliver the cancer drug. Chemical binding of high affinity ligands on the surface of the nanoparticles, enhance the interaction of nanoparticles with tumour cells, greatly improving its distribution.8 Abraxane, developed by Celgene for patients with breast cancer that has recurred or metastasized was one of the first drugs to utilise protein-bound nanoparticle technology to bind to albumin and target the cancer cells.

There are lot of other technologies also being developed, such as nanoshells to destroy a cancer cell from within using heat. I have not focused on this as it seem still to be in early research but is quite exciting. Different techniques and technologies are being used for different types of cancer, with most still being at the research stage. Another example would be nanodiamonds for the treatment of leukaemia and other forms of cancer.7

Skills Alliance has partnered with a number of clients working on the treatment of cancer via nano-therapeutic agents. One example of this is Merrimack Pharmaceuticals who have developed a compound to treat patients with various forms of cancer such as pancreatic or breast by delivering a chemotherapy drug directly to cancer cells via a liposomal nanocarrier and reducing the risk of damage to healthy cells.4 This is a very exciting new drug in development along with BIND 014 which is a prostate cancer compound, again focused on targeting antigens. In this instance, PSMA is a clinically-validated tumour antigen expressed on prostate cancer cells and the blood vessels of most non-prostate solid tumours. 10

An example of a drug delivery liposome can be seen below.5




 

In reality, this technology is still in the fairly early stages of utilisation and it is absolutely cutting edge but a number of companies are working through clinical trials and applying nanotechnology to how they target cancer cells and treat the patient. It is in my opinion one of the most exciting development for cancer treatment I have heard about and one I am going to continue to follow and support. Imagine a single device that can both identify and then destroy precancerous or cancerous cells before the tumour develops….

For more information, questions or to discuss any potential executive staffing projects across the EMEA or North America please do contact me either via email (carl.marotta@skillsalliance.com), phone (+44207 233 6202) or via Linked-in.

References:

1. Nanotechnology definition  http://www.nano.gov/nanotech-101/what/definition (Accessed on August 2015)
2. There's Plenty of Room at the Bottom by Richard P. Feynman http://media.wiley.com/product_data/excerpt/53/07803108/0780310853.pdf (Accessed on August 2015)
3. Nano therapy and cancer http://nano.cancer.gov/ (Accessed on August 2015)
4. Merrimack Pharmaceuticals pipeline - http://merrimackpharma.com/pipeline/mm-398 (Accessed on August 2015)
5. Liposome drug delivery https://en.wikipedia.org/wiki/Liposome#/media/File:Liposome.jpg (Accessed on August 2015)
6. Cancer Technology, Small but heading for the big time. http://www.nature.com/nrd/journal/v6/n3/full/nrd2285.html (Accessed on August 2015)
7. Nanodiamonds http://www.understandingnano.com/nanodiamonds-leukemia.html (Accessed on August 2015)
8. Evelina Miele et al. Albumin-bound formulation of paclitaxel (Abraxane® ABI-007) in the treatment of breast cancer. Int J Nanomedicine. 2009; 4: 99–105
9. Advances in colorectal cancer research. http://www.nih.gov/science/colorectalcancer/nanotech.htm (Accessed on August 2015)
10. BIND Therapeutics website- http://bindtherapeutics.com/pipeline/BIND014.html (Accessed on August 2015)