Functionalizing the Mesoporous Silica Shell of Upconversion Nanoparticles To Enhance Bacterial Targeting and Killing via Photosensitizer-Induced Antimicrobial Photodynamic Therapy

Core–shell nanoparticles operating by infrared-to-visible energy upconversion (UCNPs) have been proposed as theranostic carriers for photosensitizers to increase deep-tissue penetration of photodynamic therapy against tumors and bacterial infections. Herein we present a series of core–shell mesoporous silica-coated NaYF₄:Yb:Er UCNPs (mSiO₂@UCNP) with different surface functional­izations to enhance bacterial targeting and loaded with the hydro­phobic photo­sensitizer SiPc (silicon 2,9,16,23-tetra-tert-butyl-29H,31H-phthalo­cyanine dihydroxide) to boost the bactericidal effect against Gram-positive and Gram-negative bacteria upon near-infrared irradiation. Förster resonance energy transfer (FRET) from the UCNP core to loaded SiPc was facilitated, while its efficiency depended on UCNP shell functionalization, which influences the SiPc penetration depth into the mesoporous silica, constituting a convenient tool to modify FRET intensity. Functionalized UCNPs displayed dark toxicity toward Gram-negative E. coli of up to 5 orders of magnitude, while Gram-positive S. aureus viability was not decreased in the dark, offering practical means for discriminating between the two bacterial strains. Directly exciting SiPc on the UNCP led to complete eradication of E. coli and a drastic decrease of colony-forming units of S. aureus of up to 7 orders of magnitude. With this study, we demonstrate strategies to potentiate antimicrobial photodynamic therapy on nanoparticular structures that can lead to next-generation photosensitizing systems based on UCNPs to help encounter and eradicate resistant bacteria, as well as for theranostics and future in vivo applications.