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

0586565 - ÚFCH JH 2025 RIV NL eng J - Článek v odborném periodiku
van Os, W. L. - Wielaert, L. - Alter, C. - Davidović, David - Šachl, Radek - Kock, T. - Gonzalez, U. U. - Arias-Alpizar, G. - Vigario, F. L. - Knol, R. A. - Kuster, R. - Romeijn, S. - Lopez Mora, Nestor Fabian - Detampel, P. - Hof, Martin - Huwyler, J. - Kros, A.
Lipid conjugate dissociation analysis improves the in vivo understanding of lipid-based nanomedicine.
Journal of Controlled Release. Roč. 371, JUL 2024 (2024), s. 85-100. ISSN 0168-3659. E-ISSN 1873-4995
Grant CEP: GA ČR(CZ) GX19-26854X
Institucionální podpora: RVO:61388955
Klíčová slova: lipid-based nanomedicine * liposomes * fluorophores
Obor OECD: Physical chemistry
Impakt faktor: 10.8, rok: 2022
Způsob publikování: Open access

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.
Trvalý link: https://hdl.handle.net/11104/0354028