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

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dc.contributor.authorSubramaniam, S.
dc.contributor.authorJoyce, P.
dc.contributor.authorConn, C.E.
dc.contributor.authorPrestidge, C.A.
dc.date.issued2024
dc.description.abstractBacteria 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.
dc.identifier.citationBiomaterials Science, 2024; 12(13):3411-3422
dc.identifier.doi10.1039/D4BM00608A
dc.identifier.issn2047-4830
dc.identifier.issn2047-4849
dc.identifier.urihttps://hdl.handle.net/11541.2/39027
dc.language.isoen
dc.publisherRoyal Society of Chemistry
dc.relation.fundingBioplatforms Australia
dc.rightsCopyright 2024 The Royal Society of Chemistry. Access Condition Notes: Accepted manuscript available after 1 July 2025
dc.source.urihttps://doi.org/10.1039/D4BM00608A
dc.subjectantibacterial activity
dc.subjectinfections
dc.subjectnanoantibiotics
dc.titleCellular uptake and in vitro antibacterial activity of lipid-based nanoantibiotics are influenced by protein corona
dc.typeJournal article
pubs.publication-statusPublished
ror.fileinfo12286879450001831 13286879440001831 Open Access Postprint
ror.mmsid9916864426001831

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