RESUMO
Resistant bacterial infection remains a severe public health threat, and conventional antibiotic drugs work poorly in effectively treating infectious diseases. Here, we developed gallium-based nanodots (Ga NDs), consisting of specific disruption of bacterial iron ability, to treat multidrug-resistant (MDR) Gram-negative bacteria-infected diseases. The Ga NDs significantly suppress the proliferation of two typical MDR bacteria strains (P. aeruginosa and ESBL E. coli) compared with clinically used antibacterial drugs, including penicillin and levofloxacin. Ga NDs could also disrupt the biofilms of these two bacterial strains. In P. aeruginosa infected pneumonia and ESBL E. coli infected acute liver abscess models, the Ga NDs enable substantial inhibition of bacterial growth and reduce the organs' inflammation that resulted in significant improvement of survival. Further, the Ga NDs demonstrated excellent biocompatibility and biosafety characteristics. Together, we believe that our gallium containing nanotherapeutics are expected to be developed into promising alternative therapies to combat drug-resistant bacterial infection.
Assuntos
Gálio , Abscesso Hepático , Pneumonia Bacteriana , Humanos , Gálio/farmacologia , Escherichia coli , Antibacterianos/farmacologia , Bactérias , Testes de Sensibilidade MicrobianaRESUMO
Incurable implant-related infection may cause catastrophic consequences due to the existence of a biofilm that resists the infiltration of host immune cells and antibiotics. Innovative approaches inspired by nanomedicine, e.g., engineering innovative multifunctional bionic coating systems on the surface of implants, are becoming increasingly attractive. Herein, 2D black phosphorus nanosheets (BPs) were loaded onto a hydroxyapatite (HA)-coated metal implant to construct a BPs@HA composite coating. With its photothermal conversion effect and in situ biomineralization, the BPs@HA coating shows excellent performances in ablating the bacterial biofilm and accelerating fracture healing, which were verified through both in vitro and in vivo studies. Moreover, differentially expressed genes of bone formation and bone mesenchymal stem cells (BMSCs) regulated by the BPs@HA coating were identified using absolute quantitative transcriptome sequencing followed by the screening of gene differential expressions. A functional enrichment analysis reveals that the expression of core markers related to BMSC differentiation and bone formation could be effectively regulated by BPs through a metabolism-related pathway. This work not only illustrates the great potential in clinical application of the BPs@HA composite coating to eliminate bacteria and accelerate bone fracture healing but also contributes to an understanding of the underlying molecular mechanism of osteogenesis physiological function regulation based on an analysis of absolute quantitative transcriptome sequencing.