Pancreatic cancer (FP7 European project)


The SaveMe project is funded by the European Union Framework Programme 7. It is led from Israel and involves 20 Partner organizations in 9 countries (Israel, Austria, Germany, Italy, Russia, Spain, Sweden, Belgium and the UK).

The overall goal of the project is to develop novel nanoparticles that can be used to deliver imaging agents or therapeutic drugs to pancreatic cancers. Why pancreatic cancer? It is one of the most deadly of cancers with only 4% of patients surviving 5 years after diagnosis, which hasn’t changed for several decades despite improvements in the treatment of many other forms of cancer. Why nanoparticles? Nanoparticles are really particles of any composition (they can be organic or inorganic) that are in the size range of 1-100 nanometers (ie a billionth of a meter to 100 billionths of a meter). To put this in perspective, a typical human cell might be about 30 micrometers in diameter, a bacterium 1-2 micrometers – so these are less than one-tenth the size of a bacterium. This gives them some interesting properties and allows chemists and cancer biologists to put interesting things inside them and on their surfaces.

 

SaveMe figure

 

 

 

 

 

 

 

 

 

 

The SaveMe project is trying to make some very clever particles that will do certain things. One thing is that we want the finished particle to be quite big – bigger than a nanoparticle, with an outer coat of a molecule called polyethylene glycol (PEG). Big particles hang around in the body in the circulation a lot, while small particles and molecules get excreted through the kidneys into the urine. This is what happens with most drugs, they’re flushed out in a few hours. We want things that have long half-lives in the circulation. Another key feature is that we are building them to have an outer coat that can be removed by enzymes that are found in and around cancers – not only pancreatic cancers, but in fact any sort of cancers. This was where our expertise came in because we work on proteases called matrix metalloproteinases (MMPs) which are found at high levels in cancers. The nanoparticles are being designed such that one of these (MMP-9) can take off the outer coat when the nanoparticles end up in the vicinity of the tumour. This will then expose the other clever bits built onto the inner core. These nanoparticles really are going to be like Inspector Gadget!

Also, now being small – these nanoparticles can pass out of the blood vessels in the tumour – tumours have blood vessels that are not formed properly and are usually very leaky. We think they are going to accumulate there due to a phenomenon known as “enhanced permeability and retention”.

But then they have their gadgets: First off they’ll have something that will target them selectively to the surface of the tumour cells – kind of an address label for the cancer cells. Then, depending on what their job is, they may be carrying agents that will cause the pancreatic cancer to light up when the person is imaged using MRI or CT scanning in the hospital. But we are also working with our partners to make nanoparticles that will carry warheads to attack the cancers. Some will carry engineered forms of antibodies to block the functions of molecules that act on or around the surface of the cancer cells. Others will have small interfering RNAs (siRNAs) that block genes that the pancreatic cancers use to be able to grow and spread through the body. So we need for these nanoparticles to be taken up by the cancer cells and release their payload inside to kill the cells. One of our jobs has been evaluating the effects of knocking out some of the target genes with warheads, to get the best ones for building into therapeutic nanoparticles.

It’s a big project with all sorts of specialists – chemists, biologists, clinicians, radiologists, mathematicians and computer modellers. We’re all working on our different bits and we keep in contact electronically and get together every 6 months or so. We’re now into the last year of this 4 year project and it’s getting quite exciting. Certainly the project members have made some new and interesting nanoparticles that will be useful for all sorts of applications, and we know that particular bits of the grand scheme do work.