Development of polymeric theranostics using bioorthogonal chemistry.

The selective delivery and effective localization of drugs is crucial in cancer therapy. Conventional chemotherapy is subjected to certain drawbacks, such as, limitation of tumor-specific receptors that ensure efficient internalization to enhance drug release, as well as significant systemic toxicity to healthy tissues. The use of bioorthogonal chemistry is a versatile and promising tool to overcome such drawbacks, as it expands the scope of using non-internalizing receptors as targets for cancer therapy and selective release of the drug extracellularly. Importantly, the release of drug is controlled only by the addition of an exogenous molecule, limiting premature or off-target release of therapeutic. The project will utilise an extremely fast bioorthogonal click reaction; the inverse electron-demand Diels-Alder cycloaddition (IEDDA) of tetrazine and trans-cyclooctene. A hyperbranched polymer (HBP) will be synthesised that is tagged with bispecific antibodies as targeting ligands and trans-cyclooctene bearing the anti-cancer drug, Doxorubicin. This will be administered to tumour-bearing mice. Following accumulation at the tumour site, a radiolabelled (64Cu) tetrazine probe will be administered. Selective conjugation of tetrazine to the trans-cyclooctene tag of the HBP bound to the tumor will then be monitored in real-time by positron emission tomography (PET). In this way, the click reaction will facilitate pro-drug activation, as well as a means to quantify drug release in vivo.

​Gayathri Ediriweera is currently undertaking her PhD under the guidance of Asssociate Prof. Kristofer Thurecht in both the Centre for Advance Imaging and the Australian Institute for Bioengineering and Nanotechnology at the University of Queensland. She completed her B.Sc. ( Hons) from University of Sri Jayewardenepura, Sri Lanka. She received several awards including Prof. Tuley de Silva Gold medal and Alles Memorial award for her outstanding performance in B.Sc. (Hons) degree. She started her career as an Assistant Lecturer in the University of Sri Jayewardenepura, Sri Lanka. Then she received the opportunity to peruse her Doctor of Philosophy (PhD) in the University of Queensland. Her current research interest is on developing polymeric theranostics using bioorthogonal chemistry.

Key Publications

Padumadasa, C.; Abeysekara, A. M.; Thabrew, I.; Ediriweera, A. P. G. R., Pharmacological Overview of Proanthocyanidins from the Bark of Thespesia populnea (L.) as an Antioxidant and Cytotoxic Agent. International Journal of Pharmaceutical Sciences and Research 2016, 7(1), 1000-1008.

Funding

​Australian Government Research Training Program (RTP) Scholarship and UQcent Scholarship