In the frontier science fusion of synthetic chemistry and photophysics, an Australian collaboration has prepared a step change for diagnostic and therapeutic imaging.
The phenomenon of luminescence has enticed human endeavour ever since the ‘Bologna Stone’ was discovered by a 16th-century Italian cobbler, who created a glow-in-the-dark curiosity from the unusual form of barite. More than 400 years on from Vincenzo Casciarolo’s landmark alchemy, new luminescent materials are heralding the next era of innovation in medical diagnostics, communications, solar energy and numerous other technologies.
At Curtin University, Associate Professor Max Massi has assembled a diverse research team tailored for the development of advanced luminescent materials. Massi joined the University’s chemistry cohort nine years ago as an Australian Research Council Postdoctoral Fellow, and began designing and synthesising molecules for near-infrared (NIR) luminescence using lanthanoid elements. Applying their combined expertise in both organic and inorganic chemistry, the team had early success producing efficient NIR emission – a rapidly emerging area set to advance OLED technologies, night-vision devices, fibre optics and other industries.
Then, in 2013, the team’s focus shifted upon discovering molecular species with an unprecedented ability for staining cells – a microscopy technique used to better visualise cell components and metabolic processes, including those associated with pathological conditions.
“It was an unexpected and significant breakthrough, with the potential to elucidate biochemical processes related to disease progression that have been impossible to visualise,” Massi says.
The ARC gave strong support to the new research direction, awarding Massi a five-year Future Fellowship to support biosciences. This was complemented in the same year with an ARC Linkage grant to establish a state-of-the-art spectroscopy facility at Curtin.
“At the time it was a missing capability for WA’s research in the field of luminescence,” he explains.
“There were facilities in Australia, but they weren’t tailored for our specific characterisation needs, and we couldn’t routinely access them.”
From the outset, Massi’s team represented a diverse and heavily international research program, with several PhD students from European countries. The new facility enabled him to broaden the team’s research and establish strong new connections across Australia and internationally. Demonstrating the scope of collaboration, between 2011 and 2016, he co-authored 44 peer-reviewed papers with researchers from organisations including the Australian Nuclear Science and Technology Organisation (ANSTO), the University of Bologna, Italy; and the universities of South Australia, Adelaide, Queensland and Sydney.
At UniSA, chemist Dr Sally Plush was interested in developing better techniques for cell imaging, and she engaged the Curtin team to prepare and characterise a series of luminescent transition‐metal compounds. With their ability to selectively absorb colours from white light, the compounds offer significant potential as molecular markers, designed to reveal the presence of the intracellular target molecules they bind with.
Massi was subsequently invited to a UniSA seminar to discuss his team’s expertise. There, he met cell biologist Professor Doug Brooks, and before long the Curtin team were developing luminescent compounds for application in pathophysiology. This led to another unexpected breakthrough: although their focus had been protein markers, the UniSA researchers discovered that one of Massi’s new compounds stained lipids.
“Lipid staining has been a frustrating area for biologists.” Massi explains. “The compound commonly used is toxic and can’t be applied to live tissue samples.”
“It also has longevity issues – after thirty seconds the luminescence has gone, and it has a habit of attaching to non-target molecules.”
Lipids have a prominent role in many aspects of cell biology – hormone regulation, inflammation and metabolism, for example. Studies of intracellular lipids therefore inform our understanding of diverse illnesses and conditions, including metabolic disorders and obesity, neurodegenerative diseases, immune disorders, heart diseases and cancers.
However, for the reasons Massi described, studies into the cellular processes involved have been hindered by the inability to visualise lipids in live cells. The UniSA team’s chance discovery thus launched an intense research effort to develop a new compound for staining lipids in live cells. The resultant metal-based compounds are not only non-toxic, they are also resistant to photobleaching and will remain bright for days. Furthermore, they are effective for the biomolecules known as polar lipids, which include cholesterol.
“This is significant, because there’s a link between the volume of intracellular cholesterol and the stage and aggressiveness of tumours,” Massi says.
“We were able to stain live prostate cancer cells and easily see the difference in lipid content.”
Recognising a major commercialisation opportunity, in 2015, Curtin and UniSA established the joint start-up company ReZolve Scientific, which introduced five products to the diagnostics market from one patent. Two further provisional patents were obtained in 2015–16. The company then commenced promoting its products as tools for visualising cellular structure and function that will help generate new knowledge in cell biology and defining the mechanisms of disease.
Hence, diagnostics and therapeutics are set for a step change. The advance in imaging capabilities will enable new knowledge about cellular processes and the mechanisms of disease, with implications for biomedical, environmental and food sciences. Accordingly, the global science community is paying attention, and the UniSA-Curtin team has published several peer-reviewed papers in leading journals, including PLOS ONE. Testament to the products’ capabilities, the September 2016 cover of the molecular biosciences journal FEBS Letters features an impressive image from the team’s paper published in that edition.
Australia’s impact in the field of luminescence is clearly gaining momentum, helped by the timely funding support provided to Massi, whose team now has nine doctoral students. Curiously, Massi’s own research career began in Bologna, where he obtained his PhD at the Institute of Nanostructured Materials.
Just 11 years later, the Royal Australian Chemical Institute honoured his research contribution with the 2016 Organometallic Chemistry Award. Notably, the ReZolve team publicly expressed their congratulations, and added “we wouldn’t be here without his amazing science”.