(In)stability of ligands at the surface of inorganic nanoparticles: A forgotten question in nanomedicine?

Multiple inorganic nanoparticles (NPs) are currently being developed for nanomedicine. Various core materials and shapes are explored, but they all display a common hybrid structure, with organic ligands on their surface. These ligands play a key role in the NP colloidal stability and surface properties, and therefore strongly impact the biological fate of the NPs. However, ligands may be subject to reorganization, degradation, desorption, and exchange, both during their shelf-life and upon exposure to a biological environment. The question of ligand (in)stability at the surface of inorganic NPs has been little addressed in the literature. The goal of this review is to provide a portrait of this critical phenomenon. We identify and review here the different mechanisms likely to promote ligand instability and discuss the resulting biological fate of ligands. This review is aimed to provide a better understanding of these phenomena and to help researchers to design NP-based medicines with better clinical efficacy and translation ability. (c) 2022 Elsevier Ltd. All rights reserved.