Silica Coated Upconversion Nanoplatform for Ag-Based Chemo-/Photodynamic Therapy against Drug-Resistant Bacteria

Near-infrared (NIR) driven photodynamic therapy based on upconversion luminescent nanoparticles (UCNPs) is promising for fighting drug-resistant bacteria infections in deep tissues due to its good noninvasive, nonspecific, and non-drug-resistant properties, but is greatly limited by its low efficacy. Herein, honeycomb-silica-coated upconversion nanoparticles (UCNP@mSiO2) with a size of less than 100 nm were successfully prepared by a typical silica sol–gel reaction assisted with an expanding agent (p-xylene). The honeycomb silica shell has large pores with an average diameter of about 10 nm and large pore volume of 0.82 cm3/g and exhibits a MC540 loading as high as 9% in weight. The UCNP nanoparticle core can effectively capture NIR photons and activate the merocyanine 540 photosensitizer (MC540), generating reactive oxygen species to kill the drug-resistant bacteria of deep tissues. To avoid the drug prerelease, Ag nanoparticles in diameter close to that of the silica hole were covalently grafted onto the aminated UCNP@MC540@mSiO2 (UMS-NH2) nanoparticle. The Ag-decorated UMS-NH2 nanoparticles (UMSAg) showed synergistic antibacterial effects of Ag chemotherapy and photodynamic therapy and are more stable than undecorated UMS nanoparticles in an aqueous medium. The UMSAg with unreacted amino groups enhanced the binding of Ag to the bacterial membrane, effectively exerting the antibacterial effect of Ag+ and ROS. In in vitro antibacterial experiments, the killing rates of the UMSAg composite (150 μg/mL) against drug-resistant Staphylococcus aureus 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 higher than that of the sole Ag nanoparticles without irradiation. This work provides good insight for the design of efficient antibacterial agents and has a potential application for the bacterial infection of deep tissues.