Anna. C. Gemmell, Simon. Puttick, Kris. Thurecht*


Centre for Advanced Imaging and Australian Institute for Bioengineering and Nanotechnology,
The University of Queensland
Brisbane, Queensland, Australia


 The development of ‘smart’ nanomedicines capable of visualising stimuli-responsive delivery of therapeutics continues to provide a promising outlook for the future treatment of cancer. Advances in in vivo molecular imaging technology, such as MRI, PET and optical imaging, have increased our ability to successfully visualise and monitor the delivery and effect of nanomedicines in the body. However, understanding the fate of these nanomaterials in delivering therapeutic agents homogenously across a heterogeneous tumour mass in vivo remains largely unknown.

Recently, an alternative in vivo imaging technique, optoacoustic imaging (OI), has been shown to reveal important pharmacokinetic and pharmacodynamic information about nanomedicines1. By combining the high contrast of optical imaging and the high resolution of ultrasound, OI is an emerging technique that surpasses the capabilities of its constituent techniques providing superior deep tissue imaging through sensitive detection of both endogenous and exogenous probes. As has been previously demonstrated2, OI is also capable of monitoring molecular interactions through incorporation of an appropriate donor-acceptor FRET pair. Here we report on the development of novel polymeric assemblies through the synthesis of a dual stimuli-responsive amphiphilic crosslinked polymer micelle using RAFT polymerisation. This micelle was subsequently loaded with doxorubicin for cancer therapy and labelled with an optoacoustic FRET pair responsive to cell-death biomarkers, thus enabling visualisation and real-time monitoring of nanocarrier delivery, uptake and therapeutic effect in tumour tissue. Release of the drug from the micelle is enhanced through cleavage of disulfide crosslinkers, while the subsequent therapeutic effect is monitored through the evolution of an optoacoustic response as a result of FRET that arises following degradation of the nanostructure through a caspase-3-cleavable (DEVD) peptide sequence.