Good security is all about vigilance. Your body's immune system scrutinises all newcomers to weed out whatever looks suspicious and checking and rechecking ID.
In University College Dublin, Prof Ken Dawson is developing a new approach to targeting cancer, one based on using "nano" drugs that can pass repeated checks by the immune system. Dawson believes this approach could revolutionise cancer treatment.
When you take a drug, its molecules are so small that they flow to all areas of the body, mostly unchecked. The challenge Dawson faces is to send a larger drug (or drug carrier) into the body without upsetting the immune system.
This is partly about size. A nanometre is one millionth of a millimetre, and nanomedicines are on a scale similar to that of proteins, amino acids and viruses. When you are the size of a virus, you will get checked out by the body’s defences.
"What's amazing is when we get the language of the body right, as we have in a few instances, we can very precisely target cells, " says Dawson. "So far we have only made small amounts [of the nanomedicine], but we can access a tumour cell and reverse and fix it. As long as the surface of the nanoparticle is right, you can carry the necessary DNA in to do that."
Surface ID is written in peptides, but even orientation is crucial. “If you tweak the surface even a little bit, it’s the end. The body bins it,” Dawson says. The new drugs signal where they want to go, something sought for a decade. Practical benefits include cutting down nasty side effects for cancer patients.
But the challenge is always surface. Surface receptors might have several different jobs, but each one must be bang on. How to make precise drugs in quantities is a challenge for the Centre for BioNano Interactions, where Prof Dawson is director.
“Mixing everything into big pots, that isn’t going to work. We need to position parts almost particle by particle. It is more like building a car on a factory assembling line. Learning how to do it fast and precisely, that is the difficulty.”
He compares it to the early days of transistors, before perfect silicon chips manufacture with high fidelity was possible. He is confident of success, but they must go beyond tiny amounts in the lab.
“We are not trying to kill but reprogramme tumour cells,” Dawson says. “The need to go in with a hammer and crack everything up is gone. We can now play within the system by really tight rules.”
Personalised disease
The exquisitely careful build of a
nanomedicine
means that the resulting drug can treat a smaller number of patients, though with better success.
"Everybody's cancer is their own deadly personalised disease," he adds. "We will have to tailor drugs according to each person, but genetic information will help us."
Such personalised medicine relies on sequencing the DNA of target tumours and working out what script should be written on to the drug. Progress here is speeding up. In May, a team reported in Nature that it had sequenced the genome of cells from 560 tumours.
Meanwhile, Irish scientists are progressing in packaging anti-cancer drugs and diagnostics together. Profs Yuri Volkov and Adriele Prina-Mello at Trinity College Dublin recently reported using a small gold nanoparticle combined with the anticancer drug doxorubicin and a polymer called PEG [polyethylene glycol] against pancreatic cancer as part of a European project. PEG is used to avoid the body's immune system, whereas gold carries the drug and can be used to pinpoint a tumour's location. The combination improves tumour killing with reduced side effects.
Target cells
Trinity was also involved in a large EU nanomedicine project which was voted number one in the area of nanomedicine at the EuroNanoForum conference last summer. This month a follow-on project began which aims to bring multifunctional nanoparticles closer to patients.
“The hardest part is always anchoring it to the target cell itself and not a normal cell,” Volkov agrees.
Tailored nanomedicines might even require new business models. You make medicines for just several patients at a time. “It is not clear yet how this can be an industrialised process. It might be small labs preparing medicines for groups of hospitals locally,” Dawson says.
Regulators will face challenges. And assembly lines for nanomedicines will require that chemists, biologists, physicists and engineers, as well as clinicians, work together. But Dawson is optimistic: "If it works, people will find a way." Insulin pill? Not yet, but gut could be key Insulin injections are an inconvenience. Why not pop an insulin pill?
“Insulin isn’t able to cross the gut very well and it gets broken down by stomach acid and intestinal enzymes,” explains Prof David Brayden at UCD, whose lab is working to make oral insulin possible. He and his Irish Research Council-funded student Joanna Heade are working with AnaBio Techologies Ltd to encapsulate insulin in a food material, including whey protein found in foodstuffs like milk.
“The idea is that microparticles made from food-derived materials can protect insulin, and can promote its uptake if we can incorporate other suitable ingredients.”
This would be more than convenient. If insulin crosses via the intestine, it will hit the liver much more readily. “When diabetics inject themselves every day, insulin can build up in peripheral organs and that leads to weight gain and so on. Getting insulin directly to the liver through the gut is a big advantage,” Prof Brayden explains.
Prof Brayden's lab is part of a big picture, a large European-funded project testing up to 50 different nanoparticles to see which is best at delivering insulin and other similar peptides. The French pharma company Sanofi is a major player in the project.
In a project funded by the Department of Agriculture, Prof Brayden has wrapped up small tripeptides found in milk and muscle into a nanoparticle and shown that the peptides cross the gut of rat and can lower their blood pressure.
“Because we are using food grade materials as the delivery system, it should be easier to get such materials into a human trial than for chemicals that have not been approved for human use,” he adds.