Colours of Biotechnology: Nanoshells – small shells with a big future
A Gold Biotechnology Article
With one in three people expected to develop cancer during their lifetime, the challenge presented in treating the disease is now larger than ever. However, discoveries on a microscopic scale may yield important results for future therapeutics. A new technique using light, heat and ‘nanoshells’ (tiny gold-coated beads) is showing big potential in the fight against cancer.
The concept of nanoshells was first proposed by Naomi Halas and colleagues from the Department of Electrical and Computer Engineering, Houston, USA, in a 1998 issue of Chemical Physics Letters.  In it they describe tiny metallic structures they term nanoshells, measuring no more than a few hundred nanometres in width (10,000th of a centimetre). These nanoshells could be ‘designed’ to absorb specific bands of light energy, dependent on the thickness of their core and shell, and convert this energy into heat. [1,2] This heat energy can then be released into the nanoshell’s immediate surroundings, generating intense temperatures of over 40°C.
But why would Halas’s nanoshells be of such interest to scientists researching potential cancer treatments? Firstly, thanks to a phenomenon called the ‘enhanced permeability and retention effect‘, these nanoshells preferentially accumulate in cancerous tissues. This is believed to be due to the increased vascularisation found surrounding tumours and the fact that such networks tend to be leaky due to their fast development.  Importantly, this means that the nanoshells can be transported passively to the cancerous tissue to perform their heat-induced effect (figure 1).
Studies carried out on squamous cell carcinoma have already shown malignant tumours to be vulnerable to lower heat intensities than healthy tissue,  meaning that once at the tumour site, the heat generated by these nanoshells could potentially kill the cancer cells without harming the surrounding healthy tissue in the process (a benefit lacking in chemotherapy treatment which fails to discriminate between the two). This selectivity has been demonstrated in canine models of brain tumours,  but further work is needed to determine the optimum temperature for selective destruction of cancerous cells without any ‘collateral’ damage to neighbouring healthy cells. 
By controlling which bands of light energy the nanoshells absorb, nanoshell therapy may prove safer than radiation or chemotherapy. A number of research groups have been able to programme nanoshells to absorb near infrared light, which is harmless to humans.  Near infrared light is also able to penetrate through several centimetres of mammalian tissue, meaning that this form of light could be delivered to the nanoshells at the tumour site non-invasively (figure 1).  By tagging radioactive or fluorescent markers onto nanoshells, the whole process could be further guided by imaging the tumour prior to activating the nanoshells. Using gadolinium tagged nanoshells, whole tumours have already been imaged effectively using both magnetic resonance and X-ray scans in mouse models of cancer (figure 2). 
Halas’s nanoshells may be small but their potential as a cancer treatment is ever increasing. The properties of nanoshells means that they may one day be able to deliver targeted heat treatment using safe light energy directly to the site of a tumour, killing the cancer cells whilst leaving the surrounding healthy tissue unharmed. In future research, it will be important to define exactly how much heat is needed to selectively kill the cancerous tissue and how best to transfer this technique from laboratory to clinic. Nanoshells are certainly proving to be one ‘hot topic’ in cancer therapy research, so let’s make cancer sweat.
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