A Tailored Artificial Biocatalyst for Bacterial Endophthalmitis Therapy via Enhanced Ferroptosis‐Like Death

Abstract Bacterial endophthalmitis is an ophthalmological emergency that can lead to permanent blindness, and high‐efficiency therapeutic strategies that can completely eradicate pathogens within a short timeframe are needed. However, intrinsic limitations of this disease, such as low administration frequency and dosage, render most currently available nano‐antibacterial strategies inapplicable. To address this challenge, a bio‐targeted catalytic strategy that is based on a bacteria‐specific artificial biocatalyst (MoS 2 /Fe@mercaptophenylboronic acid@hyaluronic acid, MFBH) and suitable for treating bacterial endophthalmitis is proposed. The results show that MFBH exhibits high‐efficiency peptidoglycan‐targeted catalytic antibacterial capacity against both standard and clinically isolated strains of Staphylococcus aureus . Notably, the in vivo results demonstrate that MFBH achieves effective treatment of bacterial endophthalmitis at an extremely low dose (≈4 µg kg −1 ) via a single intravitreal injection without causing retinal damage. Importantly, the therapeutic efficacy of MFBH is comparable to that of vancomycin. Mechanistic analysis reveals that MFBH induces enhanced ferroptosis‐like bacterial killing by accelerating reactive oxygen species (ROS) burst. Further investigations show that the generation of abundant ROS is closely associated with the sulfur vacancies and exposed of reactive Mo 4+ on the surface of the prepared artificial biocatalyst. In summary, this bacteria‐specific artificial biocatalyst provides a promising strategy for treating endophthalmitis.