Aptamer-guided upconversion nanoconstructs enable proximity-dependent and precise photodynamic therapy for...

Methicillin-resistant Staphylococcus aureus (MRSA) infections lead to slow wound healing, but treating these wounds with conventional photodynamic therapy (PDT) remains challenging because they induce non-specific oxidative damage on healthy tissue, thereby hindering wound repair. To achieve efficient antibacterial activity while avoiding non-specific tissue injury, we constructed a DNA aptamer functionalized upconversion nanoplatform (UC@PEI-RB@Apt) for spatially confined, proximity-dependent antibacterial of MRSA. Here, upconversion nanoparticles (UCs) convert near-infrared (NIR) light into visible light, activating polyethyleneimine-modified Rose Bengal (RB) to generate ROS. Crucially, the modified aptamers act as a specific molecular anchor, enabling the nanoplatform to directly adsorb onto the bacterial surface. This generates a proximity-dependent killing effect, wherein lethal ROS are generated around the bacteria to eliminate them, while sparing surrounding healthy cells due to the short lifespan of ROS. In vitro, UC@PEI-RB@Apt exhibited excellent targeting and biofilm disruption ability, with 99.9% bactericidal efficiency. In vivo, the MRSA infected wound model confirmed that this localized treatment significantly reduced bacterial load and accelerated wound closure compared to non-targeted controls. Additionally, histological analysis confirmed excellent biosafety with negligible damage to normal skin or major organs. This study proposes a precise, aptamer-guided targeted strategy that effectively balances high bactericidal activity with tissue safety for managing drug-resistant infections.