Katie Fegan dives into the science behind gold nanoparticles for photothermal cancer therapy.
Just like Goldilocks, cancer cells are happiest when the temperature is just right. Around 37 °C, to be precise. If the temperature within a tumour rises just a few degrees centigrade higher, proteins within the tissue denature, triggering apoptosis—otherwise known as programmed cell death. Our bodies use apoptosis to eliminate old and diseased cells in a controlled manner without inducing inflammation. Using a process called photothermal therapy (PTT), scientists are now harnessing the power of heat to selectively cook, and therefore kill, cancer cells. But how does PTT work, and could it revolutionise the way we treat cancer?
PTT uses light-absorbing molecules to increase the temperature of pathologic tissue. These molecules, or photothermal agents, convert light (photo) energy to heat (thermal). By embedding photothermal agents inside a target tumour and exposing the area to laser light, researchers are able to induce a controlled temperature change (40-44 °C) within the tumour microenvironment. The process essentially creates a tiny oven in the body, where the laser is the power supply and the photothermal agents are the heating elements.
Now, you wouldn’t want hot air to uncontrollably leak out of the oven in your kitchen; your house would get very hot very quickly and your energy bill would skyrocket. The same energy-saving principles apply for PTT. If heat were to seep from the tumour, the surrounding healthy tissues could be damaged in the process. Equally, more laser power would be needed to compensate for the lost energy. Fortunately, the PTT “oven” can be optimised by refining both the power supply and heating elements.
Take the light source, for instance. While lasers are capable of delivering photons of light with pinpoint accuracy, tumours are often located deep within the body. To ensure the light reaches the target destination and is not instead absorbed by normal tissue, light from the near-infrared (NIR) region of the electromagnetic spectrum is used. PTT agents must therefore be able to absorb NIR light.
It turns out that the gold standard for a PTT agent could really be, well, gold! The noble metal displays extraordinary photothermal properties at the nanoscale. The surface electrons of gold nanoparticles (AuNPs) resonate extremely well with NIR light thanks to a phenomenon called surface plasmon resonance. In fact, AuNPs can absorb light up to 100,000 times more strongly than some of the best light-absorbing dye molecules on the market. Furthermore, their tiny size—around 1,000 times smaller than the average cancer cell—allows them to sneak inside a tumour via its rather holey supply of blood vessels, resulting in targeted delivery of AuNPs to the disease site.
What makes AuNPs such an exciting prospect in PTT is their versatility. Their ability to absorb NIR light is directly related to their shape and size. A whole host of quirky geometries have been synthesised in the laboratory to exploit this phenomenon. From nanorods to nanostars, researchers can fine-tune the NIR absorption band of AuNPs to maximise heat production. What’s more, AuNPs form stable chemical bonds with many of the body’s biomolecules. Certain protein receptors are expressed exclusively by cancer cells. By coating the surface of AuNPs with the complementary molecules (ligands) that activate these receptors, researchers can selectively target, and therefore deliver, AuNPs to the tumour site.
PTT has shown great promise in pre-clinical research, but it has yet to become a staple treatment in the clinic. Research in animal models shows that PTT is a mild, minimally invasive process that maximises cancer cell death whilst minimising damage to healthy tissue. Compare this to chemotherapy, which wreaks havoc on the entire body by disrupting the cell-division cycle, everywhere. The unpleasant side effects associated with chemotherapy, such as hair loss and nausea, are arguably as famous as the treatment itself.
Nevertheless, PTT has its own drawbacks. Nanotoxicological screening studies performed in the laboratory have drawn conflicting conclusions regarding AuNP toxicity. Further studies investigating the long-term effects of AuNPs on the body are needed before PTT can make its way into the clinic.
PTT has the potential to transform the way we treat tumours going forward. Chemotherapy might currently be taking gold in the race against cancer, but there is certainly a golden future ahead for PTT.
From Issue 21