Golden shot at cancer cure
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Tiny lumps of gold are being used to minimise the side effects of chemotherapy, to tailor existing cancer treatments to individual needs and to melt tumours with a sudden blast of heat.
Musing on the properties of gold, Professor Mostafa El-Sayed says that it must have been given to us by God to find uses for. According to Professor El-Sayed – a US National Medal of Science laureate and among the world’s leading nanoscience researchers – a large piece of gold may well be beautiful to look at, but it is on the nanoscale that its incredible chemical and physical properties emerge.
Gold nanoparticles – particles of gold between 1nm and 100nm in size – have been used since the times of ancient civilisations in stained glass, lustre plates and other ornaments thanks to the intense colouration they offer. For instance, the Lycurgus Cup - crafted in fourth century Rome - has a small number of gold nanoparticles dispersed through its glass, which sometimes appears ruby red and at other times avocado green.
Now, millennia later, these same gold specks are finding new uses as tools in emerging cancer therapies. Researchers have cobbled together an arsenal of weapons with which to fight cancer, but every treatment has its failings. Surgical interventions are restricted to large, accessible tumours; radiotherapy burns healthy tissues; chemotherapy destroys healthy cells and causes devastating side effects like nausea and hair loss. As the search for less painful therapies continues, interest is growing in gold nanoparticles as a versatile tool in cancer therapies, both for targeting existing therapies to reduce collateral damage, and as the basis of a new therapy which melts tumours.
Unlike other materials, gold is chemically unreactive and consequently one of the safest elements you can put inside a human body. It also has an enormous surface area-to-mass ratio – a dice-sized cube filled with gold nanospheres would have a surface area comparable to that of a football field – and its particular surface chemistry means that it can be easily functionalised.
This combination of properties renders gold ideal for targeting therapies; useful materials (such as cancer-seeking antibodies) can be packed on to a gold nanoparticle’s massive surface. Inside the body, the functionalised gold nanoparticle is drawn towards the tumour, where it could be made to release a chemotherapy drug, radionuclide or other agent. The localised agent causes far less collateral damage than when it is simply injected into the bloodstream.
According to Professor Kate Vallis, who leads the radiotherapeutics and radioimaging group at the University of Oxford, gold nanoparticles could prove valuable in the much-hyped shift towards ‘personalised medicine’, whereby treatments are tailored to every patient’s needs.
“The nanomedicine approach, including gold nanoparticles, fits in with that strategy because what you attach can be modular or modified,” she says. “It’s safe in the human body and manipulating it chemically to attach things to the surface is relatively simple.”
Vallis and her group have functionalised gold nanoparticles, which take advantage of the over-expression of epidermal growth factor in many types of cancer. Her gold nanoparticles carry peptides and radionuclides to the tumour, causing the gold to become locked to the cancer cells and dragged inside where it releases the radionuclide.
Other approaches combine targeted gold nanoparticles with separately injected therapeutic agents. US-based nanomedicine company CytImmune, for instance, has developed a ‘tumour-targeted Trojan horse’ based on gold nanoparticles, which binds to a tumour’s ‘leaky’ and newly formed blood vessels and destroys those cells. Chemotherapy drugs injected subsequently are able to enter the tumour more easily. CytImmune is aiming to begin a clinical trial for patients with pancreatic cancer later this year.
“We might be able to not only be more effective in reducing tumour burden, but also use less follow-on chemotherapy to kill cancer,” says Dr Lawrence Tamarkin, president and CEO of CytImmune. “By using less chemotherapeutic drug, the patient might experience [fewer] toxic side effects.”
‘With chemotherapy the patient suffers a great deal; we hope [gold] can replace chemotherapy.’
While functionalising gold to target tumours could play an important role in rendering current treatments more bearable, a completely new therapy is in the works thanks to the optical – rather than chemical – properties of gold nanoparticles.
This proposed therapy is called photothermal therapy, as it is based on the photothermal effect: light targeted at a material can cause heating. According to Professor Vincenzo Amendola, a nanotechnology expert at the University of Padova, the photothermal effect for gold is expressed through surface plasmon resonance (SPR), in which electrons surrounding the nanoparticle violently vibrate in resonance with the light. This is the same mechanism that gives gold intense colouration to gold nanoparticle‑infused ornaments such as the Lycurgus Cup.
Gold nanoscale shells, stars, rods and other objects experience SPR at different frequencies of light. For instance, gold nanoshells emit heat when blasted with visible light; but given that human bodies are not transparent this is hardly useful for targeting tumours. El-Sayed and his group found that an elongated rod shape was perfect for achieving SPR in gold with near infrared (NIR) frequency light. Crucially, NIR light can travel through what he calls ‘the mushy stuff’ (skin, tissue and blood) and, due to its low frequency, is not harmful like the high-energy X-rays and gamma rays used in radiotherapy today.
When placed inside a tumour and blasted with NIR light, these gold nanorods emit a very intense burst of heat on the picosecond scale, minimising collateral damage while melting, vaporising or deteriorating the surrounding cancer cells when the tissue temperature exceeds 42-44°C.
“You inject [gold nanoparticles] to where the cancer is, then the whole region becomes very hot and it melts the cancer cells. They disappear. They’re gone,” says El-Sayed. “Some of the cells try to move away [...] to go somewhere else and build their own cancer network there. But if you use this technique it even melts the ‘legs’ of the cancer so the cells cannot move. This is important because cancer migration is a big thing [...] this method does not allow the migration of cancer cells, and that’s actually more important than treating it because it is the migration that eventually kills people.”
El-Sayed first tested this in mice in the US, before moving on to larger mammals in Egypt. All animal tests so far have proved successful, melting the tumours and leaving the cats, dogs and horses “running around like mad” years later with no sign of relapse. If photothermal therapy works as well in humans as it does in animals, El-Sayed says, it could eventually render current treatments obsolete. “This does it better than chemotherapy, and it does not kill the person. Chemotherapy reacts with the body chemically, and therefore the patient suffers a great deal,” he says. “We hope this can replace chemotherapy.”
The prospect of undergoing gruelling cancer therapies can, for many patients, be as frightening as the disease itself. Harnessing the chemical and physical properties of gold at the nanoscale could not only improve current approaches to cancer therapies with more targeted and personalised treatments, but also opens up the possibility of a new type of therapy which could crush tumours for good.
Work with gold nanoparticles is just one part of the vast, growing field of nanomedicine. However, thanks to their glowing set of properties, these specks of gold have the potential to reshape how every type of cancer is treated.
Researchers at the University of Edinburgh are exploiting otherwise unused properties of gold to chemically activate an anti-cancer drug inside the tumour itself as many times as necessary.
“Using the chemical properties of gold we can synthesise drugs in the place that is needed, inside of the tumour,” explains Dr Asier Unciti-Broceta, reader in pharmaceutical chemistry at the University of Edinburgh.
This is achieved by sealing gold nanoparticles in a matrix to prevent proteins inside the body binding to the surface of the gold. The device is implanted into the tumour through surgery or – in the future – targeting mechanisms. The patient ingests a drug precursor, which is activated when it meets the gold catalyst in the tumour.
Not only does this localise treatment and minimise the side effects of the drug; it also allows for the tumour to be treated over and over, even if it returns years later.
“Today with focal therapies you place a radioactive seed in the tumour, and once that radioactivity is gone it’s useless,” says Unciti-Broceta. “But in our strategy you place the device in the tumour then you can be treating the person as many times as you wish.”
This could increase the tragically short life expectancy of patients with stubborn cancers such as glioblastomas, he says. This brain cancer – which always returns – could be treated again and again using the same implant. Already, Unciti-Broceta and his colleagues have seen encouraging results in tests in zebrafish, and plan to move to trialling the device in large mammals; ideally dogs, which suffer brain cancers similar to our own. A little added bonus, he says, could be that dog owners may finally get a treatment for brain cancers in their furry friends.