ABSTRACT The treatment of drug‐resistant bacterial infections remains a formidable challenge, especially in deep tissues where drug delivery is severely limited. There is an urgent need for antibacterial strategies that enable in vivo deep‐tissue imaging while minimizing resistance development. Second near‐infrared (NIR‐II) fluorescence imaging‐guided photothermal therapy, endowed with deep‐tissue penetration, high spatiotemporal resolution, and a non‐invasive bactericidal mechanism, presents a promising alternative to conventional antibiotics. However, current NIR‐II organic phototheranostic agents often struggle to achieve both high fluorescence brightness and photothermal conversion efficiency (PCE), owing to competitive photophysical processes at the single‐molecule level. Moreover, the lack of pathogen‐specific recognition modules further restricts their applicability in complex infectious microenvironments. Herein, we optimized a pentamethine cyanine fluorophore, PC1050, with an absorption maximum near 1064 nm using a structure‐modulation strategy. A counterion pairing strategy was introduced to significantly enhance both the fluorescence brightness and PCE of PC1050. Furthermore, counterion‐paired CPC1050 was co‐assembled with zinc‐dipicolylamine (Zn‐DPA) bearing varied alkyl chains to form intelligent nanoparticles, CPC1050/Zn‐DPAs, capable of selectively eradicating Gram‐positive and/or Gram‐negative bacteria. These nanoparticles not only provide a powerful platform for precise visualization and treatment of deep‐seated infections but also open new avenues for the development of personalized antibacterial therapies with minimal resistance risk.
Kong et al. (2026) studied this question.