Pegylated phospholipid micelles induce endoplasmic reticulum-dependent apoptosis of cancer cells but not normal cells

ACS Nano
Jing WangWei Liang

Abstract

The rapid developments in nanotechnology have brought with them a deep concern over the safety of nanomaterials. Investigating the molecular mechanisms underlying their toxicity in different cell lines will help us better understand and apply nanomaterials appropriately. Poly(ethylene glycol)-phosphoethanolamine (PEG-PE) is an FDA-approved nonionic diblock copolymer and is widely used in drug delivery systems. Here, we find that PEG-PE accumulates in the endoplasmic reticulum (ER) and induces ER stress and that cancer cells and normal cells have different cell fates as a result of this stress. In A549 cancer cells, PEG-PE damages ER functions and triggers apoptosis by activating proapoptotic UPR signaling and high expression of cell death effector CHOP and proapoptotic Bax/Bak. In addition, PEG-PE-induced ER stress also up-regulates lipid synthesis and triggers lipid droplet formation in cancer cells. By contrast, in MRC-5 and 293T cells, high expression of the UPR feedback protein GADD34 which inhibits proapoptotic UPR signaling, and antiapoptotic Bcl-2 and Bcl-xl which down-regulate Bax/Bak, protect these normal cells from PEG-PE-induced apoptosis. When gadd34, bcl-2, or bcl-xl is knocked down, apoptosis occurs in PEG-PE-trea...Continue Reading

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Nov 26, 2015·Biomaterials·Xiaocui FangWei Liang
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