Cellular uptake and in vitro antibacterial activity of lipid-based nanoantibiotics are influenced by protein corona.

Autor: Subramaniam S; University of South Australia, UniSA Clinical and Health Sciences, Adelaide 5000, South Australia, Australia. Clive.Prestidge@unisa.edu.au., Joyce P; University of South Australia, UniSA Clinical and Health Sciences, Adelaide 5000, South Australia, Australia. Clive.Prestidge@unisa.edu.au., Conn CE; School of Science, College of Science, Engineering and Health, RMIT University, Melbourne 3000, Victoria, Australia., Prestidge CA; University of South Australia, UniSA Clinical and Health Sciences, Adelaide 5000, South Australia, Australia. Clive.Prestidge@unisa.edu.au.
Jazyk: angličtina
Zdroj: Biomaterials science [Biomater Sci] 2024 Jun 25; Vol. 12 (13), pp. 3411-3422. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1039/d4bm00608a
Abstrakt: Bacteria have evolved survival mechanisms that enable them to live within host cells, triggering persistent intracellular infections that present significant clinical challenges due to the inability for conventional antibiotics to permeate cell membranes. In recent years, antibiotic nanocarriers or 'nanoantibiotics' have presented a promising strategy for overcoming intracellular infections by facilitating cellular uptake of antibiotics, thus improving targeting to the bacteria. However, prior to reaching host cells, nanocarriers experience interactions with proteins that form a corona and alter their physiological response. The influence of this protein corona on the cellular uptake, drug release and efficacy of nanoantibiotics for intracellular infections is poorly understood and commonly overlooked in preclinical studies. In this study, protein corona influence on cellular uptake was investigated for two nanoparticles; liposomes and cubosomes in macrophage and epithelial cells that are commonly infected with pathogens. Studies were conducted in presence of fetal bovine serum (FBS) to form a biologically relevant protein corona in an in vitro setting. Protein corona impact on cellular uptake was shown to be nanoparticle-dependent, where reduced internalization was observed for liposomes, the opposite was observed for cubosomes. Subsequently, vancomycin-loaded cubosomes were explored for their drug delivery performance against intracellular small colony variants of Staphylococcus aureus . We demonstrated improved bacterial killing in macrophages, with greater reduction in bacterial viability upon internalization of cubosomes mediated by the protein corona. However, no differences in efficacy were observed in epithelial cells. Thus, this study provides insights and evidence to the role of protein corona in modulating the performance of nanoparticles in a dynamic manner; these findings will facilitate improved understanding and translation of future investigations from in vitro to in vivo .
Databáze: MEDLINE