Recently, scientists had determined that gold nanorods, and other nanostructures, can be used to target and destroy tumour cells, but cell death was thought to be caused by the high temperature produced by the light-absorbing nanoparticles. Writing in the journal of Advanced Materials (19/10/07), the Purdue team* explained their research had discovered a more complex biochemical scenario occurs. The cells are not cooked to death; death is chemically induced by an influx of calcium.
The immune system clears away particles bigger than 100 nanometres, but the gold rods are just 15x50 nanometres – about 200 times smaller than a red blood cell, so they can remain in the blood stream time enough to attach to tumour cells.
Using two-photon luminescence (a type of optical imaging that provides higher contrast and brighter images than conventional fluorescent imaging techniques) the researchers monitored the position of nanorods in real time during tumour-cell targeting.
Light shone on the gold nanorods causes them to become extremely hot, ionising molecules around them. Tumour cell membranes often have an abnormally high number of receptor sites to capture molecules of folic acid, or folate, a form of vitamin B desired by many tumour cells. So the researchers attached folate to gold nanorods to target the receptors and attach to the membranes. Ji-Xin Cheng, an assistant professor at the school, said the cells were then illuminated with light in the near-infrared range. ‘This light can easily pass through tissue but is absorbed by the nanorods and rapidly converted into heat, leading to miniature explosions on the cell surface. This generates a plasma bubble (bleb) that lasts for about a microsecond, in a process known as cavitation,’ explained associate professor Alexander Wei. ‘Every cavitation event is like a tiny bomb. Then suddenly, you have a gaping hole where the nanorod was.’
Although the bleb is triggered by the nanorods, Dr Cheng said it is really caused by a complex biochemical process: ‘Extra calcium gets into the cell and triggers enzyme activity, which causes the infrastructure inside the cell to loosen, which causes the membrane blebs.’
In laboratory cultures, the team found that far less power was needed to injure cells by exposing the nanorods to near-infrared light while they are still on the membrane surface, rather than after their absorption.
‘We like to believe this opens the possibility of using nanorods for biomedical imaging as well as therapeutic purposes,’ Dr Cheng pointed out. Dr Wei is currently collaborating with the National Cancer Institute to determine the suitability of the functionalised gold nanorods for future clinical studies.
* Doctoral students Ling Tong, Yan Zhao, Terry B. Huff and Matthew N. Hansen, with assistant professor Dr Ji-Xin Wei and associate professor of chemistry Alexander Cheng.