Bacterial infection poses serious medical and public concerns. Herein, “33%IRTP” nanoparticles (NPs) are reported for in vivo bacterial infection detection and photodynamic treatment, serving as an alternative to antibiotic therapy. 33%IRTP nanoparticles have been developed by self-assembly of an ONOO– and ClO– responsive near-infrared dye “IR786S” and an amphiphilic polymer “TBD-PEG” containing a highly effective photosensitizer with aggregation-induced emission characteristics. As an energy acceptor, IR786S not only shows near-infrared emission for fluorescence imaging but also quenches both fluorescence and singlet oxygen generation of TBD-PEG, thus eliminating the phototoxicity of 33%IRTP nanoparticles in normal tissues. Once 33%IRTP NPs reach bacterial infection sites, IR786S could be decomposed by the overexpressed ONOO– and ClO– to turn on the red fluorescence and singlet oxygen generation of TBD-PEG, which offers image-guided photodynamic bacterial ablation. Considering their negligible in vivo da...