Quantifying active targeting
Associate Professor Kris Thurecht, University of Queensland
Does targeting nanomedicines to cellular proteins enhance accumulation and therapeutic efficacy compared to nanomedicines that rely on the enhanced permeability and retention (EPR) effect alone?
Can we quantify the direct contribution that a targeting ligand plays on tumour accumulation and biodistribution?
With only one exception, FDA approved nanomedicines rely on the EPR effect to enhance accumulation within diseased tissue. This is despite the fact that there is significant and extensive evidence showing that targeted nanomedicines show enhanced binding and uptake into cells that overexpress the target protein. This is most likely due to the inability to clearly define the benefits associated with spending additional resources to develop complex targeted nanomaterials, when the untargeted analogue may fulfil the required criteria. The ability to directly assess the impact that a targeting ligand can have on ultimate tumour accumulation will clearly be of benefit throughout the whole development process of new nanomedicines, and will undoubtedly rely on numerous factors, including size of nanomedicine, density of ligand, immunogenicity of the carrier etc. Utilisation of the vast expertise within the CBNS, along with ability to study many different classes of nanomaterials that are developed by CBNS groups, provides an excellent opportunity to investigate this phenomenon through a systematic and rational approach. Through development of new animal models, the accumulation and interaction of nanomedicines with tumour environment can be interrogated using advanced molecular imaging techniques, informing on design criteria for next generation targeted nanomedicines. Importantly, this will be of significance to both clinical and commercial partners.