| Title: |
Phase-Separated Liposomes Hijack Endogenous Lipoprotein Transport and Metabolism Pathways to Target Subsets of Endothelial Cells In Vivo |
| Authors: |
Arias-Alpizar, G.; Papadopoulou, P.; Flores Rios, X.; Pulagam, K.R.; Moradi, M.A.; Pattipeiluhu, R.; Bussmann, J.; Sommerdijk, N.; Llop, J.; Kros, A.; Campbell, F. |
| Source: |
Advanced Healthcare Materials, 12, 10, pp. e2202709 |
| Publication Year: |
2023 |
| Collection: |
Radboud University: DSpace |
| Subject Terms: |
Radboudumc 10: Reconstructive and regenerative medicine Biochemistry (UMC); Biochemistry - Radboud University Medical Center |
| Description: |
Contains fulltext : 294573.pdf (Publisher’s version ) (Open Access) ; Plasma lipid transport and metabolism are essential to ensure correct cellular function throughout the body. Dynamically regulated in time and space, the well-characterized mechanisms underpinning plasma lipid transport and metabolism offers an enticing, but as yet underexplored, rationale to design synthetic lipid nanoparticles with inherent cell/tissue selectivity. Herein, a systemically administered liposome formulation, composed of just two lipids, that is capable of hijacking a triglyceride lipase-mediated lipid transport pathway resulting in liposome recognition and uptake within specific endothelial cell subsets is described. In the absence of targeting ligands, liposome-lipase interactions are mediated by a unique, phase-separated ("parachute") liposome morphology. Within the embryonic zebrafish, selective liposome accumulation is observed at the developing blood-brain barrier. In mice, extensive liposome accumulation within the liver and spleen - which is reduced, but not eliminated, following small molecule lipase inhibition - supports a role for endothelial lipase but highlights these liposomes are also subject to significant "off-target" by reticuloendothelial system organs. Overall, these compositionally simplistic liposomes offer new insights into the discovery and design of lipid-based nanoparticles that can exploit endogenous lipid transport and metabolism pathways to achieve cell selective targeting in vivo. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
https://repository.ubn.ru.nl//bitstream/handle/2066/294573/294573.pdf; https://hdl.handle.net/2066/294573 |
| DOI: |
10.1002/adhm.202202709 |
| Availability: |
https://hdl.handle.net/2066/294573; https://repository.ubn.ru.nl//bitstream/handle/2066/294573/294573.pdf; https://doi.org/10.1002/adhm.202202709 |
| Accession Number: |
edsbas.FA32F372 |
| Database: |
BASE |