Engineered Lipids for Intracellular Reactive Oxygen Species Scavenging in Steatotic Hepatocytes

Isabella N. Westensee, Paula de Dios Andres, Edit Brodszkij, Pierre Louis Descours, Diego Perez-Rodriguez, Antonella Spinazzola, Rajeshwar Prosad Mookerjee, Brigitte Städler*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

1 Citation (Scopus)

Abstract

Intracellular reactive oxygen species (ROS) in steatotic cells pose a problem due to their potential to cause oxidative stress and cellular damage. Delivering engineered phospholipids to intracellular lipid droplets in steatotic hepatic cells, using the cell's inherent intracellular lipid transport mechanisms are investigated. Initially, it is shown that tail-labeled fluorescent lipids assembled into liposomes are able to be transported to intracellular lipid droplets in steatotic HepG2 cells and HHL-5 cells. Further, an antioxidant, an EUK salen–manganese derivative, which has superoxide dismutase-like and catalase-like activity, is covalently conjugated to the tail of a phospholipid and formulated as liposomes for administration. Steatotic HepG2 cells and HHL-5 cells incubated with these antioxidant liposomes have lower intracellular ROS levels compared to untreated controls and non-covalently formulated antioxidants. This first proof-of-concept study illustrates an alternative strategy to equip native organelles in mammalian cells with engineered enzyme activity.

Original languageEnglish
Article number2400816
JournalSmall
Volume20
Issue44
ISSN1613-6810
DOIs
Publication statusPublished - 1 Nov 2024

Keywords

  • antioxidant
  • intracellular ROS
  • liposomes
  • steatosis

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