Lipid Phase Separation in Vesicles Enhances TRAIL-Mediated Cytotoxicity

Timothy Q. Vu, Justin A. Peruzzi, Lucas E. Sant'Anna, Eric W. Roth, Neha P. Kamat*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Ligand spatial presentation and density play important roles in signaling pathways mediated by cell receptors and are critical parameters when designing protein-conjugated therapeutic nanoparticles. Here, we harness lipid phase separation to spatially control the protein presentation on lipid vesicles. We use this system to improve the cytotoxicity of TNF-related apoptosis inducing ligand (TRAIL), a therapeutic anticancer protein. Vesicles with phase-separated TRAIL presentation induce more cell death in Jurkat cancer cells than vesicles with uniformly presented TRAIL, and cytotoxicity is dependent on TRAIL density. We assess this relationship in other cancer cell lines and demonstrate that phase-separated vesicles with TRAIL only enhance cytotoxicity through one TRAIL receptor, DR5, while another TRAIL receptor, DR4, is less sensitive to TRAIL density. This work demonstrates a rapid and accessible method to control protein conjugation and density on vesicles that can be adopted to other nanoparticle systems to improve receptor signaling by nanoparticles.

Original languageEnglish (US)
Pages (from-to)2627-2634
Number of pages8
JournalNano letters
Volume22
Issue number7
DOIs
StatePublished - Apr 13 2022

Keywords

  • Janus particles
  • TRAIL
  • lipid domains
  • liposomes
  • phase separation
  • vesicles

ASJC Scopus subject areas

  • Bioengineering
  • Chemistry(all)
  • Materials Science(all)
  • Condensed Matter Physics
  • Mechanical Engineering

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