04 September 2019

Litmus for the tumor

Detection of cancer in the early stages increases the survival and quality of life of the patient. But screening studies often require expensive equipment, and a trip to a specialized clinic is difficult or even impossible for residents of rural or developing areas with poorly developed medical infrastructure. Therefore, scientists are working to create cheaper, faster and easier-to-use diagnostic tests.

An international team of engineers from King's College London and the Massachusetts Institute of Technology has developed a diagnostic system that changes the color of urine in the presence of cancer.


Urine turns blue in the presence of colon cancer in a mouse. Source here and below: Imperial College London/MIT.

A growing and metastasizing tumor produces biological signals (biomarkers) that doctors use to detect and track the disease. However, not all biomarkers play an active role in tumor growth, most of them are present in such small quantities that they are difficult to identify.

A family of tumor proteins known as matrix metalloproteinases (MMPs) has attracted the attention of researchers as potential biomarkers, since these enzymes stimulate the growth and spread of tumors by destroying the tissue scaffolds that should hold cells in place.

In this study, the group developed nanosensors in which ultra-small gold nanoclusters (AuNC) were linked to a protein carrier through bonds that are destroyed by the MMP9 tumor enzyme.


Diagnosis of bowel cancer using AuNC-protein complexes.

To develop a color-changing urine test, the researchers used two properties of AuNC: small size (less than 2 nanometers) and the ability to turn blue during chemical treatment and the addition of hydrogen peroxide.

After release from the AuNC-protein complex, destroyed by MMP9 in the tumor or blood microenvironment, AuNC with blood flow enter the kidneys and, due to their small size, are filtered into the urine.

In healthy mice without high levels of tumor enzymes, the AuNC-protein complexes remain intact and too large to penetrate into the urine.

In the experiment, the researchers injected nanosensors into 28 mice, 14 of which had colon cancer, the rest were healthy. It has been demonstrated that the color change test reliably determines which urine samples were taken from mice with colon tumors. Chemical treatment of urine took about half an hour.

The team also upgraded the AuNC so that the immune system does not react to them, thus not causing immune reactions or toxic side effects and sticking to the AuNC of a large amount of serum proteins – this would make the nanosensors too large for filtration by the kidneys.

Within four weeks after the introduction of the nanosensor, the mice did not have any side effects, as well as signs that nanosensor complexes or free AuNCs were retained in the mice.

Before the technology can leave the laboratory, there is still work to be done on optimization and numerous tests. The researchers plan to work on increasing the specificity and sensitivity of the diagnostic system by testing it on other animal models to assess accuracy and safety.

Article by C. N. Loynachan et al. Renal clearable catalytic gold nanoclusters for in vivo disease monitoring is published in the journal Nature Nanotechnology.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Imperial College London: Colour-change urine test for cancer shows potential in mouse study.

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