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

Advanced Materials, vol. 36, pp. e2310872

Abstract

The 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.

Authors 15

1. Panagiota Papadopoulou Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

   Leiden University

   Affiliation as printed

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

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

2. Rianne van der Pol Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

   Leiden University

   Affiliation as printed

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

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

3. Niek van Hilten Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

   Leiden University

   Affiliation as printed

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

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

4. Winant L. van Os Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

   Leiden University

   Affiliation as printed

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

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

5. Roy Pattipeiluhu Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

   Leiden University

   Affiliation as printed

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

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

6. Gabriela Arias‐Alpizar Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

   Leiden University

   Affiliation as printed

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

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

7. Renzo A. Knol Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

   Leiden University

   Affiliation as printed

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

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

8. Willem E. M. Noteborn Aachen

   Leiden University

   Affiliation as printed

   NeCEN Leiden University Einsteinweg 55 Leiden 2333 AL The Netherlands

   NeCEN Leiden University Einsteinweg 55 Leiden 2333 AL The Netherlands

9. Mohammad‐Amin Moradi

   Eindhoven University of Technology

   Affiliation as printed

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

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

10. Johannes M. F. G. Aerts Aachen Department of Medical Biochemistry Leiden Institute of Chemistry

    Leiden University

    Affiliation as printed

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

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

11. Nico A. J. M. Sommerdijk

    Radboud University Nijmegen · Radboud University Medical Center · Eindhoven University of Technology

    Affiliation as printed

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

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

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

12. Frederick Campbell Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

    Leiden University

    Affiliation as printed

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

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

13. Herre Jelger Risselada Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

    Leiden University · TU Dortmund University

    Affiliation as printed

    Department of Physics Technical University Dortmund 44221 Dortmund Germany

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

    Department of Physics, Technical University Dortmund, 44221 Dortmund, Germany

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

14. G. J. A. Sevink Aachen Department of Biophysical Organic Chemistry Leiden Institute of Chemistry

    Leiden University

    Affiliation as printed

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

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

15. Alexander Kros corresponding Aachen Department of Supramolecular and Biomaterials Chemistry Leiden Institute of Chemistry

    Leiden University

    Affiliation as printed

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

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