Our research group has a strong interest in the synthesis, medicinal chemistry, and chemical biology of boron and Lanthanoid elements with an emphasis on chemical probe and drug discovery, and the design of new (radio)theranostic agents.
We look to exploit the unique properties of boron and Lanthanoid elements in cutting-edge cancer therapies, and their incorporation into unique molecular scaffolds for binding to important biological receptors or as new biological fluorophores.
Our research has received funding from organisations including the Australian Research Council, The Prostate Cancer Foundation of Australia, Cure Cancer Australia Foundation and The National Breast Cancer Foundation. Our current research is also funded by an ARC Industrial Transformation Training Centre for the Development of Advanced Radiochemical Technologies (DART).
Boron-based drugs are increasingly being investigated in many disease categories. Numerous pharmaceutical companies (e.g. Pfizer, GSK, and Takeda) have dramatically expanded their boron research programs in recent years in the quest for novel drug candidates, e.g. Velcade® (bortezomib), which is used in the treatment of multiple myeloma.
In contrast, the use of polyhedral boranes in chemical probe discovery is only in its infancy. Our group is internationally recognised for this field of research and we are actively investigating the use of carboranes and other unique boron moieties in the design of new chemical probes, antimicrobials, and anticancer drugs.
We have recently designed a new class of organic chelators that can selectively target tumour cell mitochondria. These chelators can deliver high concentrations of these metal ions to tumour cells with high selectivity over normal, healthy cells.
There now exists the opportunity to exploit this family of chelators in a number of cutting-edge cancer therapies [photon activation therapy (PAT), neutron capture therapy (NCT), neutron capture enhanced particle therapy (NCEPT), and targeted radiotherapy] and also in tumour diagnosis (PET, SPECT and MRI) involving a variety of medically-relevant metal ions (e.g. Gd3+, Ga3+, Sc3+, Tb3+ and Lu3+).
The radiolabelling of selected chelators is conducted with collaborators at UNSW, UWA and ANSTO (Lucas Heights).
The 5-year survival rate for patients afflicted with aggressive and intractable brain tumours (gliomas) is very low. In this project, we will incorporate Gd3+ions into tumour-selective agents in order to localize this metal near a critical sub-cellular organelle for application in binary cancer therapies, such as photon activation therapy (PAT) and neutron capture therapy (NCT).
We have already demonstrated substantial and selective brain tumour cell destruction in the presence of a prototype Gd agent and synchrotron X-ray photons, the first time that GdPAT experiments have ever been conducted in Australia.
The use of Gd agents to target tumour cell mitochondria would open up new vistas in binary cancer therapies, with potential imaging applications using MRI.
Fluorescently-labelled molecules are invaluable tools in microscopy. There is a continuing need to develop new fluorophores, particularly those that emit in the near-IR, and those in which chemical properties can be easily tuned.
This project involves the rational design and synthesis of new boron-containing fluorophores, their photophysical characterisation and biological studies (with Prof. Liz New). For example, we have recently developed a new biological stain for lipids and sub-cellular organelles.
If you are interested in joining the Rendina research group then please contact Professor Lou Rendina directly.
