Lipid conjugate dissociation analysis improves the in vivo understanding of lipid-based nanomedicine

Lipid conjugates have advanced the field of lipid-based nanomedicine by promoting active-targeting (ligand, peptide, antibody), stability (PEGylation), controlled release (lipoid prodrug), and probe-based tracking (fluorophore). Recent findings indicate lipid conjugates dissociating from nanomedicin...

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Bibliographic Details
Published in:	Journal of controlled release Vol. 371; pp. 85 - 100
Main Authors:	van Os, Winant L., Wielaert, Laura, Alter, Claudio, Davidović, David, Šachl, Radek, Kock, Thomas, González, Urimare Ugueto, Arias-Alpizar, Gabriela, Vigario, Fernando Lozano, Knol, Renzo A., Kuster, Rick, Romeijn, Stefan, Mora, Nestor Lopez, Detampel, Pascal, Hof, Martin, Huwyler, Jörg, Kros, Alexander
Format:	Journal Article
Language:	English
Published:	Netherlands Elsevier B.V 01-07-2024
Subjects:	Dissociation Fluorophores Lipid conjugate Lipid-based nanomedicine Liposomes Zebrafish PBS PB PEG Fluorophores Zebrafish Lipid-based nanomedicine Liposomes Dissociation Lipid conjugate
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Summary:	Lipid conjugates have advanced the field of lipid-based nanomedicine by promoting active-targeting (ligand, peptide, antibody), stability (PEGylation), controlled release (lipoid prodrug), and probe-based tracking (fluorophore). Recent findings indicate lipid conjugates dissociating from nanomedicine upon encountering a biological environment. Yet, implications for (pre)clinical outcomes remain unclear. In this study, using the zebrafish model (Danio rerio), we investigated the fate of liposome-incorporated lipid fluorophore conjugates (LFCs) after intravenous (IV) administration. LFCs having a bilayer mismatch and relatively polar fluorophore revealed counter-predictive outcomes for Caelyx/Doxil (clearance vs. circulating) and AmBisome-like liposomes (scavenger endothelial cell vs. macrophage uptake). Findings on LFC (mis)match for Caelyx/Doxil-like liposomes were supported by translational intravital imaging studies in mice. Importantly, contradicting observations suggest to originate from LFC dissociation in vivo, which was investigated by Asymmetric Flow Field-Flow Fractionation (AF4) upon liposome-serum incubation in situ. Our data suggests that LFCs matching with the liposome bilayer composition – that did not dissociate upon serum incubation – revealed improved predictive outcomes for liposome biodistribution profiles. Altogether, this study highlights the critical importance of fatty acid tail length and headgroup moiety when selecting lipid conjugates for lipid-based nanomedicine. [Display omitted]
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0168-3659 1873-4995 1873-4995
DOI:	10.1016/j.jconrel.2024.05.034