Development of Bioorthogonal Smart Polymers for Quantitative Therapeutic Delivery
Dr Gayathri Ediriweera, Postdoctoral Research Fellow (Thurecht Group),
Centre for Advanced Imaging, The University of Queensland presents:
Development of Bioorthogonal Smart Polymers for Quantitative Therapeutic Delivery
Despite significant effort directed towards the development of new platforms for cancer diagnosis and treatment, it still remains as the second major leading cause of death worldwide. The efficacy of existing therapeutic systems is limited by challenges such as determining the actual drug release profile in vivo, as well as reducing side-effects for an increased standard of care for patients. Consequently, there is an unmet need to develop approaches that allow a better understanding of the pharmacokinetic/pharmacodynamic behaviour of nanomedicines and their therapeutic cargo. The use of bioorthogonal chemistry is a versatile and promising tool to address these challenges, as it can be tailored to develop theranostic systems where the drug release is controlled by the addition of an exogenous molecule, providing more direct control over drug release and minimising off-target effects.
The primary objective of our project was to perform “click-to-release” bioorthogonal trans-cyclooctene and tetrazine reaction-based prodrug activation of polymer-drug conjugates by developing a modular and controlled theranostic system that can quantitatively assess site-specific drug activation and deposition from a nanocarrier, in particular, a hyperbranched polymer. The exploitation of quantitative imaging using positron emission tomography (PET) together with pre-targeted bioorthogonal chemistries in this system, provides an effective means to assess in real-time the exact amount of active drug administered at precise sites in living species.
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