Multifunctional cerium-based nanozymes as moonlighting protein mimics for atherosclerosis diagnosis and therapy

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 heat treatment. The nanozyme possesses both superoxide dismutase (SOD) and catalase (CAT) activities, enabling scavenging of reactive oxygen species (ROS) and modulation of 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 loaded 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 application potential in various fields.