A new test using advanced nanomaterials could speed up diagnostics for a range of major human diseases. During the final stages of protein synthesis in cells, short chains of sugars known as glycans are attached, a process known as glycosylation. This creates glycoproteins, and a huge number of variants known as glycoforms.
A substantial body of evidence now exists suggesting that the process of glycosylation is subtly altered during the development of several major human diseases, including cancer and diseases of the heart and brain. Distinctive glycoforms are produced in the cells of ill patients, presenting an opportunity for the early and accurate detection of disease.
“If we can selectively detect the glycoforms associated with the disease, we are then capable of diagnosing the disease with high accuracy and at an early stage,” says Paula Mendes, professor of Advanced Materials and Nanotechnology at the University of Birmingham.
Creating moulds for glycoforms
While some glycoforms of a protein are associated with disease, others are not. Unfortunately, tools that can discriminate between these sugars have been lacking.
Current tests use antibodies to detect the presence of these altered sugars, but antibody tests are unstable, require special handling procedures, and consequently are time-consuming and costly. There are also a very limited number of antibodies that exist which can bind to sugars.
This was the driving force behind the EU-funded GLYCOSURF project, supported by the European Research Council, which developed a brand-new molecular test based on advanced materials capable of recognising specific glycoforms.
GLYCOSURF’s approach draws on advances in nanomaterials, chemistry and a technique known as molecular imprinting. This creates a mould of specific glycoforms on the surface of the nanomaterial, meaning only these sugar molecules can enter. They are easily picked up, revealing the exact underlying problem and avoiding confusion. During the project, the team developed, improved and successfully demonstrated the test’s ability to detect these specific sugars.
“These unprecedented capabilities allow us to develop much more accurate diagnostic tests for the early and accurate diagnosis of many diseases, including cancer,” Mendes explains.
The materials developed through the project are robust, stable and can be easily upscaled for industrial production, Mendes explains. This means they could be used in a wide range of biological and medical applications, and help to diagnose diseases even in settings with limited healthcare provision.
“The development of such highly precise molecular platforms for glycoprotein detection was challenging and required persistence and ingenuity,” says Mendes. “However, the research team rose to the challenge confidently and our major outcomes have been achieved,” she adds.
Reinventing the test for prostate cancer
The team are now translating the technology into a test for the early detection of aggressive prostate cancer, offering a far more accurate and reliable method than is currently available.
The most widely used tests detect a glycoprotein – prostate-specific antigen (PSA) – associated with prostate cancer, but high levels of this glycoprotein can be present for unrelated reasons. As a result, there are many false positives which cause undue stress on patients and unnecessary burdens on healthcare systems.
GLYCOSURF’s new test only picks up the few specific glycoforms of the PSA glycoprotein that are elevated when a patient has prostate cancer, meaning the result is almost certain. It can also reveal how aggressive a cancer will be, depending on the composition of the various glycoforms. Treatment can therefore be tailored to specific patients, depending on the severity of their illness.
This new endeavour is being carried out with the support of Prostate Cancer UK, with the hope of moving to clinical trials in the near future. The team also hopes to develop specific tests for a range of cancers, along with other serious non-communicable diseases.
The new diagnostic technology is being presented as part of the ‘Living with Cancer’ exhibition, held in the Manchester Science and Industry Museum last year. The exhibition is moving to the London Science Museum, remaining there from May 2022 until Jan 2023.