A Conjugated Oligomer\nwith Drug Efflux Pump Inhibition\nand Photodynamic Therapy for Synergistically Combating Resistant Bacteria

High expression of drug efflux pump makes antibiotics\nineffective\nagainst bacteria, leading to drug-resistant strains and even the emergence\nof “superbugs”. Herein, we design and synthesize a dual\nfunctional o-nitrobenzene (NB)-modified conjugated oligo-polyfluorene\nvinylene (OPFV) photosensitizer, OPFV-NB, which can depress efflux\npump activity and also possesses photodynamic therapy (PDT) for synergistically\novercoming drug-resistant bacteria. Upon light irradiation, the OPFV-NB\ncan produce aldehyde active groups to covalently bind outer membrane\nproteins, such as tolerant colicin (TolC), blocking drug efflux of\nbacteria. The minimum inhibitory concentration of antibiotic model\nchloramphenicol (CHL) is reduced about 64 times, significantly resensitizing\ndrug-resistant bacteria to antibiotics. Also, the probe can produce\nhighly efficient reactive oxygen species (ROS) under light irradiation.\nConsequently, the unimolecular OPFV-NB-based system demonstrates insusceptibility\nto antibiotic resistance while maintaining significant antimicrobial\neffects (100%) against drug-resistant bacteria. More importantly, <i>in vivo</i> assays corroborate that the combined system greatly\naccelerates wound healing by eradicating the bacterial population,\ndampening inflammation, and promoting angiogenesis. Overall, the OPFV-NB\nnot only counteracts antibiotic resistance but also holds tremendous\nPDT efficiency, which provides a promising therapeutic strategy for\ncombating drug-resistant bacteria and treating bacteria-infected wounds.