Photosensitizing Quantum Dot Killers Encoded by Bivalent DNA for Sequential Cell Penetration, Intracellular Bacterial Imaging, and Targeted Elimination

The precise identification and efficient in situ eradication of intracellular bacteria can not only prevent the bacteria from persisting and spreading within the host but also accelerate the healing of infected wounds and decrease the caused complications. In this study, we designed a multifunctional quantum dot (QD) killer equipped with aggregation-induced emission (AIE) photosensitizers and heterobivalent DNA sequences with the capability to specifically target, fluorescently image, and efficiently eliminate intracellular bacteria. These QD killers undergo cell penetration following lipopolysaccharide receptor-mediated endocytosis and then translocate to the cytosol for intracellular bacterial recognition and labeling. Additionally, by leveraging the robust photodynamic activity of sensitizing QD killers, the complete eradication of intracellular bacteria was realized by reducing the viability of the infected macrophages. The cytocompatibility of QD killers ensures safe treatment without harming normal host cells. Notably, bacterial-infected wounds in vivo showed accelerated healing rates following successful bacterial elimination with QD killer administration. This work highlights the potential of QD killers in eradicating intracellular bacteria hidden within immune cells, providing a promising strategy for addressing intracellular infection-relevant diseases.