Ligand Layer Engineering To Control Stability and Interfacial Properties of Nanoparticles.

The use of mixed ligand layers including poly(ethylene glycol)-based ligands for the functionalization of nanoparticles is a very popular strategy in the context of nanomedicine. However, it is challenging to control the composition of the ligand layer and maintain high colloidal and chemical stability of the conjugates. A high level of control and stability are crucial for reproducibility, upscaling, and safe application. In this study, gold nanoparticles with well-defined mixed ligand layers of α-methoxypoly(ethylene glycol)-ω-(11-mercaptoundecanoate) (PEGMUA) and 11-mercaptoundecanoic acid (MUA) were synthesized and characterized by ATR-FTIR spectroscopy and gel electrophoresis. The colloidal and chemical stability of the conjugates was tested by dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), and UV/vis spectroscopy based experiments, and their interactions with cells were analyzed by elemental analysis. We demonstrate that the alkylene spacer in PEGMUA is the key feature for the controlled synthesis of mixed layer conjugates with very high colloidal and chemical stability and that a controlled synthesis is not possible using regular PEG ligands without the alkylene spacer. With the results of our stability tests, the molecular structure of the ligands can be clearly linked to the colloidal and chemical stabilization. We expect that the underlying design principle can be generalized to improve the level of control in nanoparticle surface chemistry.