Sunday 4th February 2018, is World Cancer Day, a global initiative founded by the Union for International Cancer Control (IUCC). The aim of this annual event is to raise awareness and education about cancer and to unite the world in the fight against these deadly diseases. Neutron scattering is one tool used by scientists in advancing our knowledge of cancer. Recently scientists have been using the SANS2D instrument at ISIS to address the challenge of getting anti-cancer drugs directly to their target site without damaging healthy cells.
According to statistics from Cancer Research UK, every two minutes someone in the UK is diagnosed with Cancer. Chances are every one of us has - or knows someone who has – suffered from this group of diseases. The demand for solutions is higher than ever.
Cancer refers to more than 200 types of disease, caused by abnormal cells dividing uncontrollably and invading nearby tissues. It can affect anyone, of any age, gender or nationality and is responsible for nearly 1 in 6 deaths worldwide.
As a result, a lot of time and money has been channelled into developing anticancer drugs. Whilst the scientific community has enjoyed many successes, there are also many challenges. In Hoelder et al's 2012 review for the journal of Molecular Oncology, the authors highlight the many hurdles that scientists face when developing new pharmaceuticals, even referring to the gap between basic research and new drug approval as the 'Valley of Death'. Whilst the concept of harnessing small molecules such as organoiridium as highly potent anticancer drugs has been a popular choice thus far, there are many unfortunate roadblocks to this approach; namely caused by their poor solubility, rapid elimination and limited stability in the body upon testing.
The big question is; how do you safely deliver these anti-cancer drugs directly to their target site in the body? Three words; Drug. Delivery. Vectors.
Imagine the human body as a complex, multifaceted highway system. Drug delivery vectors are a form of transport. They carry goods to the target destination. They're like a car – with a Sat Nav. By delivering anticancer drugs directly to the tumour site, this molecular 'GPS' system can reduce side effects and improve the therapeutic efficiency of drugs. Carriers provide a protective shell, enhancing solubility and slowing down clearance from the blood stream. They can be optimised for both passive targeting to tumours via the enhanced permeability and retention effect (EPR) and functionalised for active targeting of specific cells.
Despite the advantages that cyclic peptide nanotubes provide, so far, only a handful of examples of their use as drug delivery vectors have been reported. In conducting their research, a team of scientists - led by Sébastien Perrier from the University of Warwick – hoped to change this. By synthesising novel cyclic peptide-polymer conjugates that are able to carry organoiridium anticancer complexes directly to target tumour cells, the team has paved the way for the use of these selective kinds of drug-bearing nanotubes in anti-cancer therapy.
Cyclic peptides were conjugated to a biocompatible polymer known as pHPMA. This acts like the vehicle whilst the organoridiium anticancer complex added to it resembles the cargo the vehicle carries. Their results have shown that not only do drug-loaded nanotubes exhibit more potent anti-proliferative activity towards human ovarian cancer cells than either free drug or drug-loaded polymers, but also that these nano-tubes are themselves non-toxic, providing a safer alternative to more traditional approaches.
Figure 1: Measuring the A) Synthesis B) Self-assembly and C) Cytotoxicity of Cyclic Peptide-Polymer Nanotubes (Larnaudie et al, 2017)
So where does neutron scattering fit in? Sans2d is a purpose-built instrument for small-angle neutron scattering (SANS), which is used to study everyday materials and biological systems in a highly efficient manner. An experimental technique originating in the 1930's, SANS makes use of the wave properties of neutrons to probe the structure of materials. Such is the precision of this process, is that scientists can examine the size, shape, internal structure and spatial arrangement within nanomaterials on length scales of between 0.25-300nm (to put that into perspective, a human hair is about 100,000nm in diameter!). This makes it incredibly useful for the study of the self-assembly of conjugates used in this experiment and confirming their characteristic cylindrical shape.
Research examples like this one highlight how neutron science, such as that undertaken at ISIS, is helping to tackle some of the greatest challenges of the 21st century. In the fight against cancer, this couldn't come any sooner.
Further information
Information regarding World Cancer Day 2018 can be found on the Cancer Research UK website.
The full publication mentioned in this article is available to view in the Journal Biomacromolecules
For further information about the research, please contact Professor Sebastien Perrier (s.perrier@warwick.ac.uk)
To learn more about SANS2D and its capabilities, please follow this link
To read more news releases concerning ISIS, please visit ISIS News
