Moonlighting proteins are multifunctional proteins widely present in organisms, playing crucial roles in various physiological activities. Drawing inspiration from the moonlight proteins，we developed a cerium (Ce)-based nanozyme CF, featuring multiple enzymatic activities along with robust cargo-loading and transport capabilities. The CF was synthesized through a one-step assembly between Ce3+ and a phosphorylated amino acid derivative, achieving high biostability through a simple heating treatment. The nanozyme possesses both superoxide dismutase (SOD) and catalase (CAT) activities, enable to scavenge reactive oxygen species (ROS) and modulate inflammation by inhibiting NF-κB pathway activation. Besides its enzymatic activities, CF can also serve as a versatile nanocarrier for various cargoes through one-pot co-assembly. Herein, the CF-based nanoassembly loading with a near infrared fluorescent dye was demonstrated to work well for the diagnosis of atherosclerotic plaques. The nanoassembly co-assembled with probucol exhibited superior ROS-scavenging and anti-inflammatory effects compared to either CF nanozyme or probucol, attributed to the synergy of the nanozyme and the drug, thus facilitating a highly efficient treatment of atherosclerosis. This work introduces a novel Ce-based nanozyme with multifunctional properties, providing a promising approach to endow nanozymes with moonlighting protein-like characteristics, thereby enhancing their functional capabilities and broadening their applications potential in various fields.
