Biomimetic Bacteriophage‐Like Particles Formed from Probiotic Extracts and NO Donors for Eradicating Multidrug‐Resistant Staphylococcus aureus

Abstract Effectively clearing multidrug‐resistant bacteria through nonantibiotic treatments is crucial for the recovery of infected tissues in favorable biological environments. Herein, a thermally responsive donor of cell‐messenger nitric oxide (NO) is combined with extracts of food‐grade Lactobacillus casei to form biomimetic phage‐like microparticles with a tailspike structure. These particles can invade bacterial membranes and release NO to disrupt nitrogen and respiratory metabolisms, which initiates the programmed death of multidrug‐resistant Staphylococcus aureus (MRSA) for inducing lysis, like the bacterial virus. Experiments suggest that these microparticles can also weaken bacterial toxicity and provide favorable conditions for cell proliferation because of the continuously released NO. By encapsulating these microparticles into graphene‐oxide‐doped polymers, a dual‐mode antibacterial hydrogel (DMAH) can be constructed. In vivo results reveal that the DMAH achieves a long‐time sterilization of MRSA with 99.84 ± 0.13% antibacterial rate in the dark because of the phage‐like performance of the biomimetic microparticles. In its other antibacterial mode, DMAH subjected to 20 min of near‐infrared irradiation release NO, which, together with the photothermal effect, synergistically damages bacterial cell membranes to achieve very fast disinfection (97.13 ± 0.41% bactericidal rate). This multifunctional hydrogel can also significantly accelerate wound healing due to the phage‐like particles.