Cancer is a leading cause of death worldwide and has a substantial social and economic impact on individuals, families and the community. Non-invasive biomedical detection of specific cancer biomarkers at the molecular level in cancer cells and cell organelles holds the key for improved cancer diagnosis and the study of cancer processes.
“Endogenous formaldehyde, produced by numerous biochemical process, is a critical factor for tissue cancerisation, cancer progression, and metastasis. Recent investigations revealed that the cell lysosomes may contribute to the generation and metastasis of endogenous formaldehyde. Current available bioassay methods cannot detect endogenous formaldehyde biomarkers in situ. This encouraged us to pioneer a new bioanalytical probe for quantitative detection of lysosomal formaldehyde in cancer cells and tumours,” explained Dr Zhang.
The team of researchers from Dalian University of Technology, Stanford University, and The University of Queensland developed a responsive luminescence probe with a unique “dual-key-and-lock” design that performs as a powerful diagnostic tool to interrogate the mechanism of formaldehyde biomarker production and its action during cancer progression and treatment. This new probe, Ru-FA, and the techniques used in its development have exciting potential applications in future biomedical research and (pre)clinical cancer early diagnosis and treatment response monitoring.
“To design the responsive probe for lysosmal formaldehyde detection, we proposed a new strategy referred to as ‘dual-key-and-lock’. The luminescence probe ‘lights up’ when it detects formaldehyde (first ‘key’) in an acidic microenvironment (second ‘key’). The luminescence intensity correlates to the formaldehyde concentration, allowing quantitative detection of formaldehyde in acidic microenvironments, such as cell lysosome with pH4.5–6.0,” explained Dr Run Zhang.
“Visualisation of tumour-derived endogenous formaldehyde and monitoring of formaldehyde scavenging by exogenous drugs were successfully demonstrated using our responsive probe.”
The luminescent cancer cell images were taken by Jianping Liu using ANFF-Q’s Leica SP8 confocal microscope. The images provide direct evidence that excessive formaldehyde serves as a biomarker for tumours. The lysosomes of cancer cells contribute significantly to the production of tumour-derived formaldehyde.
“These images clearly indicate the feasibility of our probe for lysosomal formaldehyde detection in cancer cells. We appreciate the ANFF-Q’s staff Dr Elena Taran and Dr Kinnari Shelat for their training and suggestions on taking high-resolution luminescent cell images,” said Jianping Liu.
This research, published in Journal of the American Chemical Society, has led to an effective bioanalytical method for quantitative monitoring of cancer formaldehyde biomarkers in vitro and in vivo. Successful translation of this bioanalytical technology to a diagnostic tool will advance biomedical research and early diseases diagnosis and treatment monitoring in the future.
“The unique “dual-key-and-lock” design of Ru-FA also demonstrates a promising strategy for the development of other responsive probes, especially transition metal complex-based luminescence probes for sensing and imaging of biomolecules-associated diseases,” said Dr Run Zhang.
“Our results also demonstrated that tumours produce highest level of formaldehyde (1.4–fold higher than the level in the brain), followed by the brain. The higher concentration of endogenous formaldehyde in the brain may contribute to the various activities such as memory and cognition processes, which needs to be further studied,” Dr Zhang continued.
“Future work on this project will optimise and standardise this new probing technology to deliver a diagnostic tool for cancer biomarkers detection. Further investigations of the biological roles of formaldehyde within body will also be involved. This research will be greatly strengthened by state-of-the-art facilities and technical support at ANFF-Q.”