Engineering functional nanoparticles for delivery in cells

The ability of DNA functionalised gold nanoparticles (AuNPs) to detect specific targets in vitro and in vivo has led to their development as suitable tools for sensing applications. However, endosomal entrapment is a common barrier in various nanoparticle delivery approaches. In this work, we present a new design strategy with the aim to enhance endosomal escape of DNA-coated AuNPs via the incorporation of a peptide that has been found to promote effective escape within cells. AuNPs are firstly modified with thiol terminated DNA strands followed by further surface functionalisation with cysteine terminated peptides. We show that optimized loading of peptides following DNA nanoparticle functionalisation of nanoparticles is feasible. DNA-peptide-coated AuNP hybrids show similar stability towards degradation by endocellular enzymes and similar specificity towards the detection of specific mRNA targets.