In recent years, there has been an increasing demand for more efficient and cost-effective ways to detect metabolites in biological samples. These metabolites, which are chemical by-products of various bodily processes, can provide vital insights into the presence and progression of diseases. Among these, 1-methyl nicotinamide (1-MNA) has garnered particular interest due to its role in signalling various health conditions, such as cancer, liver disease, and obesity.

Traditional methods of detecting these metabolites, such as mass spectrometry and nuclear magnetic resonance (NMR), are often expensive and complex, making them less accessible for widespread diagnostic use. The development of simpler, more sensitive biosensors for 1-MNA could help bridge this gap, providing a valuable tool for the early detection and management of disease.

In a recent article, researchers at the Nano Life Science Institute (WPI-NanoLSI) at Kanazawa University have made significant strides in this area. They have developed a biosensor that significantly improves the sensitivity of detecting 1-MNA in urine, even without the need for sample purification. This innovation holds the potential for more accessible and efficient disease diagnosis, particularly in conditions where 1-MNA levels are elevated. The team’s work, which has been published in Analytical Chemistry, demonstrates the use of a novel type of biosensor molecule that improves the detection process by orders of magnitude.

Currently, elevated levels of 1-MNA in the body are associated with various diseases, including cancer, metabolic disorders, and liver disease. As such, detecting these levels can provide crucial insights into a patient's health status. However, the techniques traditionally used to measure metabolite levels, such as mass spectrometry and NMR, present challenges. While effective, they require expensive equipment and intricate procedures, making them impractical for widespread clinical use. This has created a need for alternative methods that can offer both sensitivity and simplicity.

Researchers Masaya Ueno, Tomoki Ogoshi, and Atsushi Hirao, all affiliated with the WPI-NanoLSI, have tackled this issue by focusing on a class of molecules known as pillararenes. These molecules serve as a new type of biosensor that sidesteps the need for extensive purification, which is usually necessary when detecting other 1-MNA biosensing molecules. The result is an enhanced sensitivity and specificity, which could lead to more accurate detection of 1-MNA in biological samples.

1-MNA is produced in the body through the methylation of nicotinamide (Nam), a process mediated by nicotinamide N-methyltransferase (NNMT). This is part of the metabolism of vitamin B3, specifically the vitamer niacin. Elevated NNMT activity has been linked to certain cancers, and there is growing evidence that 1-MNA levels correlate with the aggressiveness of these tumours. Additionally, studies suggest that suppressing NNMT can alleviate certain disease-related symptoms. As a result, 1-MNA serves as an important biomarker for monitoring NNMT activity, which can provide valuable insights for disease diagnosis and management.

The researchers emphasise this point in their report, stating that "monitoring the NNMT expression and activity in patients by quantification of 1-MNA is important for elucidating and diagnosing their pathology." This underscores the clinical significance of the new biosensor, which could pave the way for improved diagnostic capabilities.

Previously, the research team had explored the potential of pillar[6]arene functionalised with carboxylate groups (P6AC) as a 1-MNA sensor. This molecule was found to bind to 1-MNA and inhibit fluorescence through a process known as photo-induced electron transfer. However, despite its potential, the biosensor required extensive sample purification and was unable to detect the micromolar concentrations of 1-MNA present in the culture supernatants of human cancer cells. This limitation prompted the team to seek out a more sensitive alternative.

In their latest work, the researchers investigated a new version of pillar[6]arene, this time functionalised with sulfonate groups (P6AS). This new molecule exhibited a much stronger binding affinity for 1-MNA—700 times greater than that of the P6AC variant. As a result, the P6AS biosensor was able to detect sub-micromolar concentrations of 1-MNA, even in unpurified human urine samples. This marked a significant improvement in sensitivity, allowing for more precise measurements of 1-MNA levels. However, it was noted that detection in human serum was not possible due to higher levels of autofluorescence, which interfered with the readings.

Although the detection sensitivity achieved with mass spectrometry remains higher at nanomolar levels, the throughput of the P6AS biosensor offers distinct advantages. According to the researchers, the high throughput capability of the P6AS biosensor could make it a promising tool for screening thousands of potential NNMT inhibitors. This has important implications for the development of treatments for diseases such as liver disease and cancer, where NNMT activity plays a crucial role.

The team attributes the improved sensitivity of the P6AS biosensor to the stronger acidity of sulfonate groups compared to carboxylate groups. In their concluding remarks, the researchers note that "further improvement of our strategy will contribute to high-throughput screening of NNMT inhibitors, diagnosis of liver diseases, and imaging of human cancer cells in vivo." This highlights the broad potential applications of the new biosensor, both in clinical diagnostics and in research focused on developing new therapeutic approaches.

In summary, the development of this new biosensor represents a significant advancement in the detection of 1-MNA. By improving sensitivity and simplifying the detection process, this innovation could lead to more accessible and efficient methods for diagnosing diseases associated with elevated 1-MNA levels. With further refinement, the biosensor may also play a key role in advancing treatment options for conditions such as cancer and liver disease.

Author

Isabella Sterling

Content Producer and Writer

Nano Magazine

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