Lipid nanoparticle-mediated induction of endoplasmic reticulum stress in cancer sells

Show simple item record Ghosh, Chandramouli Nandi, Aditi Basu, Sudipta 2019-08-31T09:18:13Z 2019-08-31T09:18:13Z 2019-08
dc.identifier.citation Ghosh, Chandramouli; Nandi, Aditi and Basu, Sudipta, “Lipid nanoparticle-mediated induction of endoplasmic reticulum stress in cancer sells”, ACS Applied Bio Materials, DOI: 10.1021/acsabm.9b00532, Aug. 2019. en_US
dc.identifier.issn 2576-6422
dc.description.abstract The endoplasmic reticulum (ER) primarily guides protein synthesis, folding, transport, and lipid biosynthesis inside the cells. As a result, dysregulation in those cellular functions leading to ER stress has recently emerged as one of the hallmarks of cancer. Yet, precise navigation in the ER in cancer cells has continued to be a formidable task. Herein, we engineered a lipid nanoparticle (17AAG-ER-NP) containing (a) ER targeting moiety (Tosyl), (b) fluorescent tag with DNA damaging capability (1,8-naphthalimide), and (c) ER stress inducer (17AAG, Hsp90 inhibitor). These lipidic nanoparticles were confined in the ER of HeLa cells over 6 h through caveolin-controlled endocytosis confirmed by confocal microscopy. Western blot analysis, fluorescent microscopy, and flow cytometry studies confirmed that 17AAG-ER-NPs can concurrently activate ER stress and nuclear DNA impairment for arresting the cell cycle in the G2-M phase to elicit late apoptosis, followed by cell death, in a greatly augmented manner compared to free drugs. Interestingly, this nanoparticle-mediated ER stress activated autophagy, which was suppressed through a cocktail treatment with 17AAG-ER-NPs and chloroquine (autophagy inhibitor), prompted remarkable HeLa cell killing at submicromolar concentration. This nanoplatform can support new tools to impair multiple targets in the ER for future cancer therapy. en_US
dc.language.iso en_US en_US
dc.publisher American Chemical Society en_US
dc.subject endoplasmic reticulum (ER) en_US
dc.subject ER homing en_US
dc.subject DNA damage en_US
dc.subject cancer en_US
dc.subject lipid nanoparticle en_US
dc.title Lipid nanoparticle-mediated induction of endoplasmic reticulum stress in cancer sells en_US
dc.type Article en_US
dc.relation.journal ACS Applied Bio Materials

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