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Nanogold: From Ruby-red Glass to Possible Cancer Treatment

The shiny lustre of gold has fascinated people since ancient times. But using some ingenious chemistry to produce particles of gold so small that they are measured in billionths of a meter (nanometers), opens up a whole new world.

Though aesthetically pleasing, gold is scientifically quite boring. It is chemically inert, meaning it doesn’t easily react with other chemicals and remains shiny for long periods which is why it is prized in jewelry. But when it comes to tiny pieces of gold, only nanometers long, the science becomes far more interesting. These mini metal flecks of gold nanoparticles have potentially far-reaching applications.

The Big History of Nanotechnology

In 1669, German chemist Johann Kunckel made a remarkable discovery. Adding tin chloride and a solution of gold dissolved in “aqua regia” to molten glass resulted in a stunning ruby-red colour. He didn’t know it of course, but the red colour was due to particles of nanogold. Aqua regia is a mixture of hydrochloric and nitric acids and is one of the few reagents with which cold will react. The gold chloride that forms can be converted back to gold by reaction with tin chloride, but the gold now is in the form of nanoparticles that absorb all colours of light except for red which is reflected.

Modern nanotechnology began with the invention of the scanning tunnelling microscope in 1981. This was the first time scientists could ‘see’ on the nanoscale. An atom is about 10-10 meters, and a nanometer is 10-9 meters. This means that when we talk about ‘nanotechnology’ or ‘nanoparticles’, we refer to things made of a couple of thousand atoms. The scanning tunnelling microscope also made possible the manipulation of individual atoms, which allowed scientists to create nanoparticles.

Nanoparticles are different from their smaller or larger cousins because their size and shape directly affect their chemical properties. Imagine that the way you cut your bread changed the flavour; a diagonal slice gave you cinnamon bread, but a horizontal slice changed the same piece of bread into sourdough. This is similar to what is happening on the nanoscale! A sphere of gold has different properties than a cylinder of gold, which is different from a cube despite all being made of gold. One property that changes with the size and shape of a nanoparticle is colour. A long gold nanotube will reflect red light, but a shorter nanotube will reflect turquoise-blue light, as was finally explained by Richard Adolf Zsigmondy who was awarded the 1925 Nobel Prize in Chemistry for his work on colloids, tiny insoluble particles suspended in another substance.

Now we come to a truly exciting finding. A new type of cancer treatment uses gold nanoparticles' flexible properties to kill tumour cells! Cancer is a terrifying disease. Although there have been great advances in treatment, cancer is still Canada's leading cause of death. Normal, healthy cells replicate based on copies of a genetic code. In cancerous cells, there are mutations (or typos) in the genetic code, causing erroneous replication and abnormal growth. Once cancerous cells replicate enough, they form a tumour. Tumours generate blood vessels to get nutrients and hijack our immune system to protect themselves, all at the cost of our normal, healthy cells. Because tumours are so dangerous, cancer therapies focus on destroying tumour cells with minimal damage to healthy cells. This is where gold nanoparticles come into the picture.

Cancer photothermal therapy (PTT) is a minimally invasive treatment that uses nanoparticles to convert light energy into heat energy (hence the name photo-thermal!). First, gold nanoparticles are injected into the bloodstream. To help the nanoparticles find the tumour, scientists can attach special targeting ligands that act as ‘keys’ that only fit into a tumour cell’s ‘lock’. Once the gold nanoparticles find the tumour cells, the second stage of the therapy begins.

A specific type of light, called Near Infrared Radiation (NIR), is directed at the tumour. These light waves will travel through surrounding tissue and hit the gold nanoparticles, which are specially shaped to absorb this wavelength of light. Remember how we talked about different slices of bread - or shapes of nanoparticles - having different properties? Scientists experimented with different nanoparticle shapes and found that for PTT, gold nanorods, shaped like cylinders, or gold nanocages, shaped like hollow cubes, best absorb NIR.

The last stage of PTT is possible thanks to surface plasmon resonance. This fancy terminology refers to gold nanoparticle’s ability to turn the light waves from NIR into synchronized electron movement. The synchronized electron ‘wiggles’ generate thermal energy, or heat, which is then transferred to the nearby tumour cell. Gold nanoparticles can increase the temperature around a tumour to somewhere between 41 and 47 degrees Celsius – hot enough to seriously damage tumour cells. Gold nanoparticles are great candidates for PTT because they are especially good at converting light into thermal energy.

There is some cool science behind gold nanoparticle cancer-fighting powers, but cool science in the lab doesn’t necessarily transfer to effective treatment. One of the most complex steps in drug development is jumping from experiments in cell culture or animal models to demonstrating that a treatment actually works in patients. Gold nanoparticle PTT is still in this ‘jumping’ stage, and it’s potential is difficult to predict. An initial clinical trial in prostate cancer has shown promise and other clinical trials in lung and head and neck cancer are underway. There is some uncertainty about the long-term effects of gold nanoparticles, and some worry about serious side effects.

To be sure, gold nanoparticles have come a long way from producing ruby-glass and perhaps in the future may even make for a gold standard in cancer treatment.


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