A Photomodulable Bacteriophage‐Spike Nanozyme Enables Dually Enhanced Biofilm Penetration and Bacterial Capture for Photothermal‐Boosted Catalytic Therapy of MRSA Infections

Abstract Nanozymes, featuring intrinsic biocatalytic effects and broad‐spectrum antimicrobial properties, are emerging as a novel antibiotic class. However, prevailing bactericidal nanozymes face a challenging dilemma between biofilm penetration and bacterial capture capacity, significantly impeding their antibacterial efficacy. Here, this work introduces a photomodulable bactericidal nanozyme (ICG@hMnO x ), composed of a hollow virus‐spiky MnO x nanozyme integrated with indocyanine green, for dually enhanced biofilm penetration and bacterial capture for photothermal‐boosted catalytic therapy of bacterial infections. ICG@hMnO x demonstrates an exceptional capability to deeply penetrate biofilms, owing to its pronounced photothermal effect that disrupts the compact structure of biofilms. Simultaneously, the virus‐spiky surface significantly enhances the bacterial capture capacity of ICG@hMnO x . This surface acts as a membrane‐anchored generator of reactive oxygen species and a glutathione scavenger, facilitating localized photothermal‐boosted catalytic bacterial disinfection. Effective treatment of methicillin‐resistant Staphylococcus aureus‐associated biofilm infections is achieved using ICG@hMnO x , offering an appealing strategy to overcome the longstanding trade‐off between biofilm penetration and bacterial capture capacity in antibacterial nanozymes. This work presents a significant advancement in the development of nanozyme‐based therapies for combating biofilm‐related bacterial infections.


Figure S6. A)
The X-ray photoelectron spectroscopy (XPS) spectrum of the ICG@hMnO x .

B)
The high-resolution XPS spectrum of Mn 3s in ICG@hMnO x .

Figure S7. A)
The XRD spectrum of the ICG@hMnO x .B) SAED pattern of the ICG@hMnO x .

FigureFigure S5 .
Figure S4.A) DLS profile of ICG@hMnO x in different physiological solutions (n = 4).B) Tyndall effect of ICG@hMnO x in different physiological solutions.Data are presented as mean ± s.d.

Figure
Figure S10.A) The survival rate of MRSA exposed to different concentrations of ICG@hMnO x with 808 nm laser (1.0 W/cm 2 , 5 min) irradiation (n = 4).Data are presented as mean ± s.d.B) Representative plates of MRSA exposed to different concentrations of ICG@hMnO x with 808 nm laser (1.0 W/cm 2 , 5 min) irradiation.

Figure S11 .
Figure S11.Live/dead staining of MRSA with or without POD reaction substrate H 2 O 2 .

Figure
Figure S12.A) The survival rate of MRSA incubated with ICG@hMnO x for indicated irradiation time by 808 nm laser (n = 4).Data are presented as mean ± s.d.B) Representative plates of MRSA incubated with ICG@hMnO x for indicated irradiation time by 808 nm laser.

Figure
Figure S13.A) Representative photograph of hemolytic assay of indicated samples.B) Viability of HaCaT cells treated with indicated concentrations of ICG@hMnO x (n = 4).Data are presented as mean ± s.d.

Figure S14 .
Figure S14.Trade-off between the biofilm penetration and bacterial capture capacity of manganese nanoparticles with different surface morphology.A) 3D CLSM images of the spiky ICG@hMnO x or smooth ICG-MONPs incubated MRSA biofilms.Purple: ICG from nano-formulation; green: MRSA biofilm.B) TEM images of planktonic methicillin-resistant Staphylococcus aureus (MRSA) bacteria incubated with the spiky ICG@hMnO x or smooth MONPs.

Figure
Figure S16.A) Flow cytometry analysis of reactive oxygen species (ROS) level in MRSA after different treatments.B) Relative glutathione (GSH) levels of MRSA after different treatments (n = 4).Data are presented as mean ± s.d.*P < 0.05.

Figure S17 .
Figure S17.Images of Gram's stained wound tissues harvested from different groups at 4 d post-wounding.

Figure S19 .
Figure S19.Representative immunofluorescence images of Ki67 in wound tissues harvested from different groups at 14 d post-wounding; green fluorescence indicates the expressed Ki67 in wound tissues.

Figure S21 .
Figure S21.The Mn ion content in the newly healed wound tissue and healthy skin (n = 3).Data are presented as mean ± s.d.