Multifunctional MIL-101 nanoparticles with Fenton-like reactions to Co-deliver LL-37 peptide and Vancomycin for targeted NIR imaging and Drug-resistant bacteria treatment

Abstract

Bacterial infections and antibiotic resistance have become a global healthcare crisis. There is an urgent need to develop visualized therapeutic platforms that allow accurate imaging of the bacterial infections, successful eradication of bacteria and real-time monitoring of treatment progress. In this work, we report a novel NIR imaging and synergistic antibacterial nano-system (LL-37@MIL-101-Van) for resistance bacterial infection therapy. The multifunctional nano-system is fabricated by a MIL-101 core, which is covalently connected with Vancomycin and modified with targeted antimicrobial peptides LL-37 on the surface. The ability of monitoring the progress of infection treatment and effective promoting wound healing of bacterial infection are proved by in vivo MRSA-infected mice models. Under the environment of endogenous H2O2 overexpression and slightly acid bacterial infection, the excellent Fenton-like reaction activity of LL-37@MIL-101-Van could effectively catalyze the decomposition of H2O2 to produce hydroxyl radicals (•OH), which trigger highly efficient chemo-dynamic therapy (CDT) and tissue protection effect. By combining CDT with antibacterial peptides and antibiotics therapy, special targeting and synergistic killing of MRSA are successfully achieved in in vitro and in vivo antibacterial assays with excellent biocompatibility. Due to this, this study proposes a novel, high-efficient, multifunctional imaging and therapy system, which will open a new avenue for the design of synergistic antibacterial and diagnostic platforms in the future.