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

Panagiota Papadopoulou1, Rianne van der Pol1, Niek van Hilten1

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

Advanced Materials (Deerfield Beach, Fla.)
|November 21, 2023
PubMed
Summary
This summary is machine-generated.

Researchers uncovered how triglyceride lipases interact with phase-separated lipid nanoparticles, enabling targeted delivery. This mechanism enhances nanoparticle-protein communication for advanced nanomedicine applications.

Keywords:
cell targetinglipaseslipid-based nanoparticlesmRNA-deliverynano-bio interfacephase-separated

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Area of Science:

  • Biochemistry
  • Nanotechnology
  • Drug Delivery

Background:

  • Lipid-based nanoparticles' behavior in vivo is dictated by their membrane-protein interactions.
  • Understanding these interactions is key to developing targeted nanomedicine.
  • Lipid phase separation in liposomes has previously been shown to mediate cell-selective accumulation via triglyceride lipases.

Purpose of the Study:

  • To investigate lipase-induced changes in phase-separated liposomes.
  • To elucidate the mechanism of lipase recognition and binding to these particles.
  • To engineer phase-separated mRNA-lipid nanoparticles (LNPs) for targeted delivery in zebrafish embryos.

Main Methods:

  • Investigated lipase-induced compositional and morphological changes in phase-separated liposomes containing lipid droplets.
  • Identified the specific lipase region responsible for particle binding using biochemical analysis.
  • Generated phase-separated mRNA-LNPs and tested their targeting and mRNA delivery in zebrafish embryos.

Main Results:

  • Selective lipolytic degradation of lipid droplets within liposomes was observed, with nanoparticle integrity maintained.
  • The Tryptophan-rich loop of triglyceride lipases was identified as the binding site, interacting with lipid packing defects on the liposome surface.
  • Phase-separated mRNA-LNPs successfully targeted cell subsets in zebrafish embryos, leading to mRNA delivery and protein expression.

Conclusions:

  • Lipase binding to phase-separated liposomes is mediated by specific enzyme-surface interactions at lipid packing defects.
  • Lipid droplet degradation by lipases does not compromise nanoparticle integrity.
  • Phase-separated mRNA-LNPs demonstrate potential for targeted delivery and gene expression in vivo, advancing nanomedicine.
  • Findings enhance understanding of nanoparticle-protein communication and in vivo behavior for improved control over lipid-based nanoparticles.