Entropy‐Mediated High‐Entropy MXenes Nanotherapeutics: NIR‐II‐Enhanced Intrinsic Oxidase Mimic Activity to Combat Methicillin‐Resistant Staphylococcus Aureus Infection

Abstract Bacterial infections, such as bacterial keratitis (BK) and subcutaneous abscess, pose significant challenges to global healthcare. Innovative and new antibacterial agents and antibacterial strategies are in demand to control infections in this era of high drug resistance. Nanotechnology is gradually emerging as an economically feasible and effective anti‐infection treatment. High‐entropy MXenes (HE MXenes) are used to confer desirable properties with exposed active sites to high‐entropy atomic layers, whose potential application in the field of biomedicine remains to be explored. Herein, monolayer HE MXenes are fabricated by implementing transition metals with high entropy and low Gibbs free energy to fill the gap in the biocatalytic performance of non‐high‐entropy MXenes. HE MXenes are endowed with extremely strong oxidase mimic activity (K_m = 0.227 mm) and photothermal conversion efficiency (65.8%) in the second near‐infrared (NIR‐II) biowindow as entropy increases. Subsequently, HE MXenes realize NIR‐II‐enhanced intrinsic oxidase mimic activity for killing methicillin‐resistant Staphylococcus aureus and rapidly removing the biofilm. Furthermore, HE MXenes can effectively treat BK and subcutaneous abscess infection induced by methicillin‐resistant Staphylococcus aureus as nanotherapeutic agents with minuscule side effects. Overall, monolayer HE MXenes demonstrate promising clinical application potential in the treatment of drug‐resistant bacterial infections and promote the healing of infected tissues.