A Dual-Targeted Platform Based On Graphene For Synergistic Chemo-Photothermal Therapy Against Multidrug-Resistant Gram-Negative Bacteria And Their Biofilms (Vol 393, 124595, 2020)

The construction of multimodal targeting and therapeutic platforms is a promising strategy for combating multidrug-resistant (MDR) bacteria-associated infections. We report a dual-targeted antibacterial platform integrating a synergistic chemo-photothermal effect based on the boronic acid functionalized graphene-based quaternary ammonium salt (B-CG-QAS). When located at the sites of Gram-negative bacteria associated infections, B-CG-QAS was able to specifically bind to the bacteria and their biofilms via the dual effect of electrostatic adhesion (QAS) and covalent coupling (BA), resulting in a superior targeting ability over the single-targeted agents (B-CG or CG-QAS), improved bactericidal efficacy, a reduced dose of QAS and minimized chemotherapeutic/photothermal toxicity. In addition to the QAS-mediated antibacterial effects, NIR laser irradiation onto CG could further improve the antimicrobial effect via the synergy of hyperthermia. On the other hand, QAS could disrupt the bacterial cell membrane and improve its permeability and sensitivity to heat. Moreover, B-CG-QAS could be effectively utilized for synergistic chemo-photothermal therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate bacteria-infected wound healing as well as exhibit outstanding biocompatibility both in vitro and in vivo. Therefore, our study demonstrates that B-CG-QAS has great potential to treat MDR Gram-negative bacterial infections and their biofilms.