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Color-Change Urine Test for Cancer Shows Potential in Mouse Study

Simple Test Indicates Growing Tumors

Tools that detect cancer in its early stages can increase patient survival and quality of life. But cancer-screening methods often mean expensive equipment and trips to the clinic, which may not be feasible in rural or developing areas with little medical infrastructure. Thus, the emerging field of point-of-care diagnostics is working on cheaper, faster, and easier-to-use tests. 

An international pair of engineering labs have now developed a tool that changes the color of mouse urine when colon cancer is present. The findings from testing the fast, non-invasive cancer test are published today in Nature Nanotechnology

The early stage technology, developed by teams from England’s Imperial College London and the Massachusetts Institute of Technology (MIT), works by injecting nanosensors into mice; the nanosensors are cut up by enzymes released by the tumor, known as proteases. 

Once the nanosensors are broken up, they pass through the kidney, and are visible to the naked eye after a urine test that produces a blue color change. 

The researchers applied the technology to mice with colon cancer, and found that urine from tumor-bearing mice turns bright blue, compared with test samples from healthy mice. 

Such a test can be administered without the need for expensive and hard-to-use lab instruments. According to the researchers, “the simple readout could potentially be captured by a smartphone picture and transmitted to remote caregivers to connect patients to treatment.”

In this study, the Imperial-MIT team developed nanosensors in which ultra-small gold nanoclusters (AuNCs) were connected to a protein carrier through linkages that are broken by MMP9s, a specific matrix metalloproteinase (MMP) enzyme.

To develop the color-changing urine test, the researchers used two AuNC properties––their very small (< 2 nanometer) size, and their ability to cause a blue color change when treated with a chemical substrate and hydrogen peroxide. 

The researchers designed the AuNC-protein complexes to disassemble after being cut by MMPs in the tumor microenvironment or blood. When broken apart, the released AuNCs travel via the blood and are small enough to be filtered through the kidneys into the urine. 

In healthy mice without high MMP levels, the complexes remain intact, and are too large to pass into the urine. If AuNCs have been concentrated in the urine, a chemical test will produce a blue color change that can be seen with the naked eye. 

For this study, the researchers developed sensors cut apart by particular MMPs and tested them in mice. The researchers demonstrated that their color change test could accurately detect which urine samples came from mice with colon tumors in a study of 28 mice injected with the sensors, where 14 mice were healthy and 14 had tumors. 

Within 30 minutes of the chemical treatment, only the urine from mice with tumors had a strong blue color. By contrast, urine from the healthy control mice showed no change in color.

The team also designed the AuNC surfaces to go “unseen” by the immune system to prevent immune reactions or toxic side effects, and to prevent abundant serum proteins from sticking to them, which would make the nanosensors too large to be filtered by the kidneys. 

During a four-week follow-up after nanosensor administration, the mice showed no signs of side effects, and there was no evidence that the protein-sensor complex or free AuNCs lingered in the bodies of the mice.

The researchers are now aiming to increase the specificity and sensitivity of the sensors by testing them in additional animal models to investigate diagnostic accuracy and safety. They are working on a formulation that is easier to administer, and identifying ways to make the sensors responsive to multiple biomarkers in order to distinguish between cancers and other diseases.

Source: EurekAlert!, September 3, 2019

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