Biofilms have become one of the fundamental issues for
chronic
infections, while traditional therapies are often ineffective in removing
quiescent (persister) cells from biofilms, resulting in a variety
of implant-related or nosocomial infections. Recently, bacteriophage
(phage) therapy has reflourished in research and clinical trials.
However, phage therapy alone manifested many intrinsic defects, including
poor biofilm penetration, incomplete clearance of quiescent cells,
etc. In this study, a phage-Chlorin e6 (Ce6)-manganese dioxide nanocomposite
(PCM) was constructed by mild biomineralization. The results demonstrated
that PCM contained both the vigorous activities of host bacterial
targeting and efficient delivery of Ce6 to penetrate the biofilm.
Assisted with NIR irradiation, robust reactive oxygen species (ROS)
was triggered within the biofilm. In the weak acidic and GSH-rich
infection niche, PCM was degraded into ultra-small nanosheets, endowing
PCM with moderate photothermal therapy (PTT) effects and considerable
Mn2+ release, thus exerting strong chemodynamic therapy
(CDT) effects in situ. In vivo application
demonstrated that the combination of PCM application and NIR irradiation
strikingly reduced the pathogen loading, activated innate and adaptive
immunity, promoted neocollagen rearrangement, and attenuated cicatricial
tissue formation. Our research may pave a new way for bacterial treatment,
biofilm-related infections, and other diseases caused by bacteria.