A plug and play approach for the decoration of nanoparticles with recombinant proteins

As the use of biomacromolecules as therapeutics increases, the challenge of delivering complex biopharmaceuticals, such as those based on proteins and peptides, becomes more pressing [1,2]. Nanocarriers have been traditionally decorated with proteins or peptides for targeting purposes but also for promoting cellular uptake [3] and, in the case of Abraxane, proteins themselves constitute the nanocarrier [4]. Besides the deliberate adsorption or conjugation of proteins onto nanoparticles, nanomedicines administered by intravenous injection will be exposed to high concentrations of proteins in the serum, which readily adsorb on the surface of the nanoparticles forming the so-called protein corona. It is fair to say that unless a nanoparticle has been deliberately engineered to repel proteins, all of them will adsorb proteins at some point during their journey toward the target tissue. It is now well accepted that the formation of a protein layer surrounding the nanoparticle can have significant effect on the biodistribution and the efficacy of the targeting strategy [5–8]. For this reason, the ability to carefully engineer the interface between the nanoparticle and body fluids could play a significant role in future nanomedicines [9,10]. This article focuses on the idea that designer proteins can be used to form a stable protein corona before injection and exposure to serum proteins. The use of proteins that prevent the formation of a serum protein-rich corona and carry targeting or cell penetrating domains could potentially elude opsonization, increase tissue specificity and improve the pharmacokinetics of nanocarriers [5]. However, the controlled adsorption or chemical conjugation of proteins onto nanoparticles is not straightforward and far from universal, due to the remarkable diversity of protein structures and chemistries involved. As a consequence, the conjugation method for each nanoparticle/protein pair would require extensive optimization and this is reflected by the large number of specific functionalization strategies developed so far [11,12]. As the excessive diversification of methods and chemistries in nanocarriers’ synthesis could potentially lead to regulatory complications, it is important to study modular strategies to simplify and reduce the number of molecular building blocks required. Such approach was recently reported in the context of modular assembly of proteins on gold nanoparticles [13] and it is detailed below.