Near-infrared (NIR) driven photodynamic therapy basedon upconversionluminescent nanoparticles (UCNPs) is promising for fighting drug-resistantbacteria infections in deep tissues due to its good noninvasive, nonspecific,and non-drug-resistant properties, but is greatly limited by its lowefficacy. Herein, honeycomb-silica-coated upconversion nanoparticles(UCNP@mSiO(2)) with a size of less than 100 nm were successfullyprepared by a typical silica sol-gel reaction assisted withan expanding agent (p-xylene). The honeycomb silicashell has large pores with an average diameter of about 10 nm andlarge pore volume of 0.82 cm(3)/g and exhibits a MC540 loadingas high as 9% in weight. The UCNP nanoparticle core can effectivelycapture NIR photons and activate the merocyanine 540 photosensitizer(MC540), generating reactive oxygen species to kill the drug-resistantbacteria of deep tissues. To avoid the drug prerelease, Ag nanoparticlesin diameter close to that of the silica hole were covalently graftedonto the aminated UCNP@MC540@mSiO(2) (UMS-NH2)nanoparticle. The Ag-decorated UMS-NH2 nanoparticles (UMSAg)showed synergistic antibacterial effects of Ag chemotherapy and photodynamictherapy and are more stable than undecorated UMS nanoparticles inan aqueous medium. The UMSAg with unreacted amino groups enhancedthe binding of Ag to the bacterial membrane, effectively exertingthe antibacterial effect of Ag+ and ROS. In invitro antibacterial experiments, the killing rates of theUMSAg composite (150 mu g/mL) against drug-resistant Staphylococcusaureus and drug-resistant Pseudomonas aeruginosa under NIR irradiation were 100% and 99.6%, respectively. In addition,the antibacterial activity of the UMSAg group was significantly higherthan that of the sole Ag nanoparticles without irradiation. This workprovides good insight for the design of efficient antibacterial agentsand has a potential application for the bacterial infection of deeptissues.