Researchers at the University of Pennsylvania’s School of Engineering and Applied Science have designed glycol chitosan-coated iron-oxide nanoparticles that are attracted to the acidic environments in which tumours generally thrive.
Scientists have previously attempted to design targeted contrast agents by coating nanoparticles with proteins that bind only to receptors found on the exterior of tumours.
’One of the limitations of a receptor-based approach is that you just don’t hit everything,’ said associate professor Andrew Tsourkas. ‘It’s hard to recommend them as a screening tool when you know that the target receptors are only expressed in 30 per cent of tumours.’
The new approach takes advantage of something known as the Warburg effect. Most of the body’s cells are aerobic and primarily get their energy from oxygen. However, even when oxygen is plentiful, cancerous cells use an anaerobic process for their energy, which turns glucose into lactic acid and creates a lower pH than the surrounding healthy tissue.
The change in charge that occurs in the vicinity of acidic tumours causes the iron-oxide nanocarriers to be attracted to and retained at those sites and ionised. Also, by using glycol chitosan, a sugar-based polymer that reacts to acids, the nanocarriers remain neutral when near healthy tissue.
The technique may be particularly useful in breast cancer diagnosis and treatment, Tsourkas said. Standard mammograms lack sensitivity and so can miss potentially dangerous tumours. A more sensitive technique using MRI with a gadolinium contrast agent may therefore be recommended, but this can flag up benign tumours that need no immediate treatment.
‘Having a tool such as ours would allow clinicians to better differentiate the benign and malignant tumours, especially since there has been shown to be a correlation between malignancy and pH,’ Tsourkas said.
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