Mechanism‐Guided Engineering of Upconversion Nanoparticles for Antibacterial Phototherapy: From Photonic Principles to Translational Nanosystems

ABSTRACT

The emergence of multidrug‐resistant (MDR) bacteria necessitates the development of next‐generation antimicrobial strategies beyond conventional antibiotics. Upconversion nanoparticles (UCNPs), owing to their anti‐Stokes luminescence under near‐infrared (NIR) excitation, offer a versatile platform for deep‐tissue antibacterial photodynamic therapy (aPDT). This review focuses on the fundamental photonic mechanisms of UCNPs, including rational dopant selection, core–shell structural engineering, and spectral tuning strategies. These photophysical features are closely related to energy transfer pathways to PS—such as Förster resonance energy transfer (FRET), direct excitation, and under specific interfacial conditions, Dexter exchange—to optimize reactive oxygen species (ROS) generation efficiency. We also highlight advanced nanoplatforms that integrate UCNPs with stimuli‐responsive carriers and targeting ligands, enabling site‐specific activation, synergistic antibacterial functions, and multimodal therapeutic effects. Translational prospects and unresolved challenges are further discussed, with an emphasis on mechanistic insights and design principles toward clinically relevant UCNPs‐enabled aPDT systems.