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.