TY - JOUR
T1 - Engineered Lipids for Intracellular Reactive Oxygen Species Scavenging in Steatotic Hepatocytes
AU - Westensee, Isabella N.
AU - de Dios Andres, Paula
AU - Brodszkij, Edit
AU - Descours, Pierre Louis
AU - Perez-Rodriguez, Diego
AU - Spinazzola, Antonella
AU - Mookerjee, Rajeshwar Prosad
AU - Städler, Brigitte
N1 - Publisher Copyright:
© 2024 The Author(s). Small published by Wiley-VCH GmbH.
PY - 2024/11/1
Y1 - 2024/11/1
N2 - 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.
AB - 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.
KW - antioxidant
KW - intracellular ROS
KW - liposomes
KW - steatosis
UR - http://www.scopus.com/inward/record.url?scp=85197412423&partnerID=8YFLogxK
U2 - 10.1002/smll.202400816
DO - 10.1002/smll.202400816
M3 - Journal article
C2 - 38949047
AN - SCOPUS:85197412423
SN - 1613-6810
VL - 20
JO - Small
JF - Small
IS - 44
M1 - 2400816
ER -