Development of ATP-Responsive PEGylated Ligands for Gold Nanoparticles

The use of systems based on polyethylene glycol (PEG) coronas improves the systemic pharmacokinetic profile of many nanocarriers. However, this stealth effect inherently hinders cellular internalization, compromising drug efficacy. This limitation is called the “PEG dilemma”. To overcome this obstacle, responsive platforms are currently being developed, allowing the release of PEG chains in response to specific stimuli. This project focuses on the chemical design and partial synthesis of a PEG derivative with the aim of using it as a non-covalent, ATP-responsive corona on gold nanoparticles (AuNPs). This work details part of the synthesis, successfully yielding a key intermediate after optimizing reaction conditions. Future work will focus on completing the synthesis and testing the behavior of the NPs, thus forming a system to evaluate the ATP-activated deshielding in vitro.