In a case of ancient medicine meeting post-millennial technology, researchers have found that attaching tiny gold particles to a cutting-edge new anticancer ‘cytokine’ therapy could help ‘super-charge’ the therapy even more. The research, funded by charity Worldwide Cancer Research, clears the way for the therapy’s safer use in humans. The findings were recently published in Nano Research.
Biological signalling molecules called ‘cytokines’ are made by white blood cells in the body. Cytokine-based anticancer treatments can be very effective, but they can also cause serious immune reactions in patients, limiting their use. In an effort to reduce these unwanted side-effects, a group of Milan-based researchers including Dr Flavio Curnis and Professor Angelo Corti at the Fondazione Centro San Raffaele used the latest technology to develop a new type of targeted anticancer cytokine treatment called NGR-TNF.
NGR-TNF combines a cytokine called TNF with a short ‘coded’ protein fragment called an NGR peptide. The peptide acts much like a postcode on a letter- actively directing the drug straight to tumour blood vessels where it can cause the most damage. And they’ve already had some success- a version of NGR-TNF is currently in clinical trials for patients with a rare form of cancer often caused by asbestos exposure.
But the researchers wanted to go further. In this latest study they show that attaching tiny gold ‘nanogold’ particles no bigger than a polio virus to the NGR peptide might help even more of the drug to reach the tumour.
Gold particles are easy to manipulate in size and shape, they can easily be altered chemically to attach to drugs or other nanomaterials, and have special properties which can make them especially easy to see in the body using scans and other imaging techniques.
The new super-charged NGR-TNF therapy was able to delay tumour growth in cancer-prone mice without any noticeable side-effects. This suggests the drug was able to reach active levels in tumour tissue while staying at low, safe, levels everywhere else - potentially opening the door for its use in other cancers.
"Cytokines like TNF have the potential to be very effective cancer treatments, but the high concentrations traditionally needed to kill cancer cells can also damage healthy cells" says Dr Curnis. "This means TNF is currently only used to treat patients with sarcomas in the extremities, as it cannot be administered systemically.
"We found that the NGR-TNF-nanogold based therapy was able to delay tumour growth in mice even at very low doses, and didn’t cause any unwanted toxic reactions. These new findings provide “proof-of-concept” that NGR-tagged nanogold could potentially be used systemically for low-dose cytokine delivery- hopefully with reduced side-effects."
The human body can tolerate pure gold very well. The particularly unreactive nature of gold has made it popular for all sorts of medical uses over the centuries, from smallpox cures to dental fillings. And nanomedicine researchers are still exploiting the yellow metal’s properties today. But this is the first time a nanomedicine combining the cancer-targeting powers of both the NGR peptide and gold particles has been developed.
"We believe this new nanodrug formulation could represent a second generation of NGR-TNF," says Dr Curnis. ‘The next step is now to optimize it further. Specifically, we need to improve its chemical stability and simplify the production process. It’s exciting but years of work and significant investment is still needed to bring the drug to patients."
Dr Helen Rippon, Chief Executive of Worldwide Cancer Research said: “Using gold in nanomedicines to tackle cancer is a really novel and exciting area of cancer research. This project we funded in Milan is just one example of how important it is to invest in the best ideas for cancer research, no matter where in the world they come from.
“This work is all still taking place in the lab and the next few steps needed to bring it to patients which will take time. But by using two independent mechanisms to get the drug to the tumour Dr Curnis and his team have got off to a great start developing a potentially new cancer nanotherapy.”
The work was supported by a grant from Worldwide Cancer Research, the leading UK charity funding early stage research into any cancer type, anywhere in the world. The research was also supported by Ministero della Salute of Italy, and Associazione Italiana Ricerca sul Cancro.
Research was carried out at the Fondazione Centro San Raffaele in Milan, Italy. Along with Dr Flavio Curnis and Professor Angelo Corti, other researchers who contributed to the work include Dr Anna Gasparri, Dr Martina Fiocchi and Mrs Angelina Sacchi.
Worldwide Cancer Research has invested over £199 million in research grants to some of the world’s best scientists across 34 different countries. The charity, based in St Andrews, Scotland, has 169 active projects across 22 countries.
