ABSTRACT
Acute lung injury (ALI) is a severe inflammatory lung disease, with high mortality rates. Early intervention by reactive oxygen species (ROS) scavengers could reduce ROS accumulation, break the inflammation expansion chain in alveolar macrophages (AMs), and avoid irreversible damage to alveolar epithelial and endothelial cells. Here, we reported cell-penetrating R9 peptide-modified triangular DNA origami nanostructures (tDONs-R9) as a novel nebulizable drug that could reach the deep alveolar regions and exhibit an enhanced uptake preference of macrophages. tDONs-R9 suppressed the expression of pro-inflammatory cytokines and drove polarization toward the anti-inflammatory M2 phenotype in macrophages. In the LPS-induced ALI mouse model, treatment with nebulized tDONs-R9 alleviated the overwhelming ROS, pro-inflammatory cytokines, and neutrophil infiltration in the lungs. Our study demonstrates that tDONs-R9 has the potential for ALI treatment, and the programmable DNA origami nanostructures provide a new drug delivery platform for pulmonary disease treatment with high delivery efficiency and biosecurity.
Subject(s)
Acute Lung Injury , DNA , Nanostructures , Acute Lung Injury/drug therapy , Acute Lung Injury/pathology , Acute Lung Injury/chemically induced , Animals , Mice , DNA/chemistry , Administration, Inhalation , Nanostructures/chemistry , Reactive Oxygen Species/metabolism , Macrophages, Alveolar/drug effects , Macrophages, Alveolar/metabolism , Cytokines/metabolism , Peptides/chemistry , Nebulizers and Vaporizers , Cell-Penetrating Peptides/chemistry , Disease Models, Animal , Lipopolysaccharides , Drug Delivery Systems , RAW 264.7 CellsABSTRACT
OBJECTIVES: To verify the contribution of the globally disseminated Neisseria gonorrhoeae FC428 clone to the emergence of ceftriaxone resistance in Chengdu in south-west China during 2018. METHODS: Antimicrobial susceptibility of the N. gonorrhoeae isolates to six antibiotics was determined using the agar dilution method. A real-time PCR assay and WGS were used to identify the FC428 clone. Phylogenomic and molecular antimicrobial resistance analyses were conducted to characterize the transmission and evolution of related strains. RESULTS: Four out of 112 N. gonorrhoeae isolates were confirmed as the ceftriaxone-resistant FC428 clone. Phylogenomic analysis revealed that they resulted from multiple introductions and subsequent local transmissions. The strains have undergone further evolutions characterized by the accumulation of mutations in resistance-associated genes and/or the acquisition of plasmids encoding penicillin and tetracycline resistance genes. CONCLUSIONS: The N. gonorrhoeae FC428 clone has spread to south-west China. Efforts should be made to enhance gonococcal antimicrobial surveillance to control further dissemination of this successful clone at both local and national levels.
