Assembly and biological functions of metal-biomolecule network nanoparticles formed by metal-phosphonate coordination

Metal-organic networks have attracted widespread interest owing to their hybrid physicochemical properties. Natural biomolecules represent attractive building blocks for these materials because of their inherent biological function and high biocompatibility; however, assembling them into coordination network materials, especially nanoparticles (NPs), is challenging. Herein, we exploit the coordination between metal ions and phosphonate groups, which are present in many biomolecules, to form metal-biomolecule network (MBN) NPs in aqueous solution at room temperature. Various phosphonate-containing biomolecules, including plant phytate, DNA, and proteins, were used to assemble MBN NPs with tunable physicochemical properties (e.g., size). In addition to excellent biocompatibility and high cargo-loading efficiency (>95%), these two-component MBN NPs have various biological functionalities, including endosomal escape, immune regulation, and molecular recognition, thus offering advantages over nonbiomolecular-based coordination materials. This work expands our understanding of metal-organic chemistry with the emerging class of metal-biomolecule systems and provides a pathway for incorporating biofunctionalities into advanced coordination materials for diverse fields.