Phase‐Separated Lipid‐Based Nanoparticles: Selective Behavior at the Nano‐Bio Interface

Author:

Papadopoulou Panagiota1,van der Pol Rianne1,van Hilten Niek1,van Os Winant L.1,Pattipeiluhu Roy1,Arias‐Alpizar Gabriela1,Knol Renzo Aron1,Noteborn Willem2,Moradi Mohammad‐Amin3,Ferraz Maria Joao4,Aerts Johannes Maria Franciscus Gerardus4,Sommerdijk Nico35,Campbell Frederick1,Risselada Herre Jelger16,Sevink Geert Jan Agur7,Kros Alexander1ORCID

Affiliation:

1. Department of Supramolecular & Biomaterials Chemistry Leiden Institute of Chemistry (LIC) Leiden University P. O. Box 9502 Leiden 2300 RA The Netherlands

2. NeCEN Leiden University Einsteinweg 55 Leiden 2333 AL The Netherlands

3. Department of Chemical Engineering and Chemistry Eindhoven University of Technology P. O. Box 513 Eindhoven 5600 MB The Netherlands

4. Department of Medical Biochemistry Leiden Institute of Chemistry (LIC) Leiden University P. O. Box 9502 Leiden 2300 RA The Netherlands

5. Department of Medical BioSciences and Radboud Technology Center – Electron Microscopy Radboud University Medical Center Nijmegen 6525 GA The Netherlands

6. Department of Physics Technical University Dortmund 44221 Dortmund Germany

7. Department of Biophysical Organic Chemistry Leiden Institute of Chemistry (LIC) Leiden University P. O. Box 9502 Leiden 2300 RA The Netherlands

Abstract

AbstractThe membrane‐protein interface on lipid‐based nanoparticles influences their in vivo behavior. Better understanding may evolve current drug delivery methods toward effective targeted nanomedicine. Previously, the cell‐selective accumulation of a liposome formulation in vivo is demonstrated, through the recognition of lipid phase‐separation by triglyceride lipases. This exemplified how liposome morphology and composition can determine nanoparticle‐protein interactions. Here, the lipase‐induced compositional and morphological changes of phase‐separated liposomes—which bear a lipid droplet in their bilayer— are investigated, and the mechanism upon which lipases recognize and bind to the particles is unravelled. The selective lipolytic degradation of the phase‐separated lipid droplet is observed, while nanoparticle integrity remains intact. Next, the Tryptophan‐rich loop of the lipase is identified as the region with which the enzymes bind to the particles. This preferential binding is due to lipid packing defects induced on the liposome surface by phase separation. In parallel, the existing knowledge that phase separation leads to in vivo selectivity, is utilized to generate phase‐separated mRNA‐LNPs that target cell‐subsets in zebrafish embryos, with subsequent mRNA delivery and protein expression. Together, these findings can expand the current knowledge on selective nanoparticle‐protein communications and in vivo behavior, aspects that will assist to gain control of lipid‐based nanoparticles.

Funder

Deutsche Forschungsgemeinschaft

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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