Targeted nanomedicines have significantly changed the way new therapeutics are designed to treat disease.1 The ability to integrate nanomaterials with biological components has led to the development of new generation devices, diagnostic tools and biotechnology-derived therapeutic-enhancing products. While such conjugates show significant promise as next-generation targeted nanomedicines, it is recognized that there are in fact no clinically-approved targeted therapeutics on the market. This clearly shows that more focus is needed for designing these nanomedicines. It is essential to understand the physicochemical properties of these materials, the function of each component and their interactions on a molecular level. Research to date has established some general rules for designing new nanomaterials with respect to size, shape and surface charge. However, these generalised rules seldom translate from the in vitro model to the in vivo, and there is no clear methodology for optimising targeting approaches for drug delivery vehicles. In this presentation, we report on developing an amphiphilic protein-polymer conjugate for assembly into targeted micellar structures using thermoresponsive polymer-conjugated antibodies and polyethylene glycols. By controlling the protein density of mixed micelles, the aim is to address key questions relating to optimisation of their function: 1) the effect of ligand density and 2) the effect of multiple ligand binding to surface receptors. We envisage that these studies will provide a better understanding on how ligand density and type affect targeting efficacy of micellar systems in which the targeting ligand density of more biologically relevant protein-based ligands can be controlled through the self-assembly process. This approach gives fundamental insight into how these different parameters affect the rate and mechanistic pathways into cells as well as a method to probe the intricate interplay between increased targeting efficiency versus the subsequent immune response.
