Near infrared II excitation nanoplatform for photothermal/chemodynamic/antibiotic synergistic therapy combating bacterial biofilm infections

Drug-resistant bacterial biofilm infections (BBIs) are refractory to elimination. Near-infrared-II photothermal therapy (NIR-II PTT) and chemodynamic therapy (CDT) are emerging antibiofilm approaches because of the heavy damage they inflict upon bacterial membrane structures and minimal drug-resistance. Hence, synergistic NIR-II PTT and CDT hold great promise for enhancing the therapeutic efficacy of BBIs. Herein, we propose a biofilm microenvironment (BME)-responsive nanoplatform, BTFB@Fe@Van, for use in the synergistic NIR-II PTT/CDT/antibiotic treatment of BBIs. BTFB@Fe@Van was prepared through the self-assembly of phenylboronic acid (PBA)-modified small-molecule BTFB, vancomycin, and the CDT catalyst Fe(2+) ions in DSPE-PEG(2000). Vancomycin was conjugated with BTFB through a pH-sensitive PBA-diol interaction, while the Fe(2+) ions were bonded to the sulfur and nitrogen atoms of BTFB. The PBA-diol bonds decomposed in the acidic BME, simultaneously freeing the vancomycin and Fe(2+) irons. Subsequently, the catalytic product hydroxyl radical was generated by the Fe(2+) ions in the oxidative BME overexpressed with H(2)O(2). Moreover, under 1064 nm laser, BTFB@Fe@Van exhibited outstanding hyperthermia and accelerated the release rate of vancomycin and the efficacy of CDT. Furthermore, the BTFB@Fe@Van nanoplatform enabled the precise NIR-II imaging of the infected sites. Both in-vitro and in-vivo experiments demonstrated that BTFB@Fe@Van possesses a synergistic NIR-II PTT/CDT/antibiotic mechanism against BBIs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12951-023-02212-7.