A membrane targeted multifunctional cationic nanoparticle conjugated fusogenic nanoemulsion (CFusoN): induced membrane depolarization and lipid solubilization to accelerate the killing of Staphylococcus aureusElectronic supplementary information (ESI) available: Detailed synthesis of nanoemulsions, experimental methods, 1H-NMR spectrum, AFM images of NE and CNP, stability studies, zone of inhibition images, killing kinetics plate count images, live/dead images of penicillin-treated S. aureus, AFM and DLS sizes of NECNP-treated S. aureus, stack plot of the GC-MS chromatograms, MIC and MBC values, live/dead cell viability of L929 cells and hemocompatibility and cytocompatibility of Betadine, SilverStream and Dermaklenz wound cleansers. See DOI: https://doi.org/10.1039/d3mh01102j

Autor: Bose, Somashree, Dahat, Yogita, Kumar, Deepak, Haldar, Saikat, Das, Sujoy K.
Zdroj: Materials Horizons; 2024, Vol. 11 Issue: 3 p661-679, 19p
Abstrakt: Bacterial infections caused by Staphylococcus aureusare one of the growing concerns for human health care management globally. Antibiotic-associated adverse effects and the emergence of bacterial resistant strains necessitate the development of an alternative yet effective approach. Nanoemulsion-based therapy has emerged as a potential therapeutic strategy to combat bacterial infestation. Herein, we designed a cationic metal nanoparticle-conjugated fusogenic nanoemulsion (CFusoN) as a lipid solubilizing nanovesicle for the effective treatment of S. aureusinfection with a killing efficiency of 99.999%. The cationic nanoparticle-conjugated nanoemulsion (viz.NECNP) (24.4 ± 2.9 mV) electrostatically bound with the negatively charged bacterial cell membrane (−10.2 ± 3.7 mV) causing alteration of the bacterial surface charge. The fluorometric and flow cytometry studies confirmed the bacterial membrane depolarization and altered cell membrane permeability leading to cell death. The atomic force microscopic studies further demonstrated the damage of the cellular ultrastructure, while the transmission electron microscopic image and membrane lipid solubilization analysis depicted the solubilization of the bacterial membrane lipid bilayer along with the leakage of the intracellular contents. The cell membrane fatty acid analysis revealed that the methyl esters of palmitic acid, stearic acid and octadecadienoic acid isomers were solubilized after the treatment of S. aureuswith CFusoN. The bactericidal killing efficiency of CFusoN is proposed to occur through the synergistic efficacy of the targeted attachment of CNP to the bacterial cells along with the lipid solubilization property of NE. Interestingly, NECNP didn’t elicit any in vitrohemolytic activity or cytotoxicity against red blood cells (RBCs) and L929 fibroblast cells, respectively, at its bactericidal concentration. Furthermore, a porcine skin wound infection model exhibited the enhanced wound cleansing potency of CFusoN in comparison to the commercially available wound cleansers. The obtained antibacterial activity, biocompatibility and skin wound disinfection efficacy of the NECNP demonstrated the formulation of a cell targeted CFusoN as a promising translatable strategy to combat bacterial infection.
Databáze: Supplemental Index