Zein-based Upconversion Nanoplatform enables NIR-activated Photothermal-photodynamic synergy for rapid sterilization and biofilm eradication.

Bacterial resistance is a major factor compromising the efficacy of conventional antibiotics, particularly in the treatment of biofilm-associated infections. To tackle this critical challenge and enable antibiotic-free antimicrobial therapy, we developed a near-infrared (NIR)-activated photothermal-photodynamic therapy nanoplatform (UCNPs/Cur@Zein@PDA, denoted as UCZP), through an innovative Zein-based hierarchical integration strategy. Specifically, upconversion nanoparticles (UCNPs) and curcumin (Cur) were co-encapsulated within the hydrophobic core of Zein nanoparticles through self-assembly, followed by surface polymerization of polydopamine (PDA). Under 808 nm laser irradiation, the resulting UCZP nanoplatform exhibits efficient photothermal conversion and enhanced reactive oxygen species (ROS) generation, leading to rapid bacterial inactivation within 10 min via disruption of cell wall and membrane integrity, as well as inhibition of the respiratory chain. Moreover, the UCZP nanoplatform achieves effective eradication of mature biofilms under the same irradiation conditions. Collectively, this work establishes a NIR-activated synergistic ROS-thermal antibacterial paradigm and presents a promising colloidal strategy combating biofilm-associated infections.