A/Prof Sarah Shigdar

The SLS lab is focused on developing aptamers for both diagnostic and therapeutic applications. Projects include the development of aptamers to aid in the diagnosis of tumours in pathology labs and the generation of more sensitive diagnostic tests, as well as the development of these aptamers as drug delivery vehicles. A major focus of the SLS lab is to develop these aptamers into effective agents that can cross the blood brain barrier and target brain disorders and diseases, such as Parkinson's disease, Alzheimer's disease and brain tumours. The SLS lab is always interested in pursuing collaborative partnerships to advance knowledge in the use of aptamers as theranostic agents.

'My passion is to ensure cancer patients have a better quality of life during treatment and a better prognosis following treatment'

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MY LATEST RESEARCH

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Bifunctional Aptamer–Doxorubicin Conjugate Crosses the Blood–Brain Barrier and Selectively Delivers Its Payload to EpCAM-Positive Tumor Cells

 

Abstract

The prognosis for breast cancer patients diagnosed with brain metastases is poor, with survival time measured merely in months. This can largely be attributed to the limited treatment options capable of reaching the tumor as a result of the highly restrictive blood–brain barrier (BBB). While methods of overcoming this barrier have been developed and employed with current treatment options, the majority are highly invasive and nonspecific, leading to severe neurotoxic side effects. A novel approach to address these issues is the development of therapeutics targeting receptor-mediated transport mechanisms on the BBB endothelial cell membranes. Using this approach, we intercalated doxorubicin (DOX) into a bifunctional aptamer targeting the transferrin receptor on the BBB and epithelial cell adhesion molecule (EpCAM) on metastatic cancer cells. The ability of the DOX-loaded aptamer to transcytose the BBB and selectively deliver the payload to EpCAM-positive tumors was evaluated in an in vitro model and confirmed for the first time in vivo using the MDA-MB-231 breast cancer metastasis model (MDA-MB-231Br). We show that colocalized aptamer and DOX are clearly detectable within the brain lesions 75 min postadministration. Collectively, results from this study demonstrate that through intercalation of a cytotoxic drug into the bifunctional aptamer, a therapeutic delivery vehicle can be developed for specific targeting of EpCAM-positive brain metastases.

Nucleic Acid Therapeutics. Apr 2020.117-128.http://doi.org/10.1089/nat.2019.0807

The SLS lab opened at Deakin University in 2013. The lab is run by A/Prof Sarah Shigdar, and her lab group are housed in the $15M Molecular Medicine Research Facility at Deakin University Waurn Ponds, which contains a comprehensive suite of equipment to service molecular biology, cell biology, microscopy and histology at PC2 level.