Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway

Chia-Cheng Hou,1,6 Tsung-Lin Tsai,1,6 Wen-Pin Su,6 Hsing-Pang Hsieh,7 Chen-Sheng Yeh,4,5 Dar-Bin Shieh,1–4 Wu-Chou Su1,6 1Institute of Basic Medical Sciences, 2Institute of Oral Medicine and Department of Stomatology, 3Advanced Optoelectronic Technology Center, 4Center for Micro/Nano Scien...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Hou CC, Tsai TL, Su WP, Hsieh HP, Yeh CS, Shieh DB, Su WC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/f40d5c91f2a847a4b9d0a2f25a8c332a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:f40d5c91f2a847a4b9d0a2f25a8c332a
record_format	dspace
spelling	oai:doaj.org-article:f40d5c91f2a847a4b9d0a2f25a8c332a2021-12-02T00:02:35ZPronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway1176-91141178-2013https://doaj.org/article/f40d5c91f2a847a4b9d0a2f25a8c332a2013-07-01T00:00:00Zhttp://www.dovepress.com/pronounced-induction-of-endoplasmic-reticulum-stress-and-tumor-suppres-a13797https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Chia-Cheng Hou,1,6 Tsung-Lin Tsai,1,6 Wen-Pin Su,6 Hsing-Pang Hsieh,7 Chen-Sheng Yeh,4,5 Dar-Bin Shieh,1–4 Wu-Chou Su1,6 1Institute of Basic Medical Sciences, 2Institute of Oral Medicine and Department of Stomatology, 3Advanced Optoelectronic Technology Center, 4Center for Micro/Nano Science and Technology, 5Department of Chemistry, 6Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Division of Biotechnology and Pharmaceutical Research, NHRI, Miaoli, Taiwan Background: LY294002 (LY) is a potent inhibitor of phosphatidylinositol 3-kinases (PI3Ks); however, biological applications of LY are limited by its poor solubility and pharmacokinetic profile. This study aimed at developing LY-loaded surfactant-free poly(lactic-co-glycolic acid) (PLGA) nanoparticles (SF-LY NPs) to improve the therapeutic efficacy of LY. Materials and methods: Cellular viability was measured by MTT assay. The subcellular distribution of NPs was studied using an ultraviolet-visible spectrophotometer and confocal microscope. The expression of cell-death-associated proteins was determined using Western blotting and the in vivo activity of SF-LY NPs was tested in a xenograft animal model. Results: SF-LY NPs enhanced the intracellular level of LY, induced sustained suppression of AKT, and induced marked cancer cell death. In addition, SF-LY NPs tended to accumulate in the endoplasmic reticulum (ER) and induce pronounced ER stress. Finally, SF-LY NPs exhibited a prominent antitumor effect in vivo. Conclusion: The surfactant-free formulation of PLGA is critical to the promising anticancer activity of SF-LY NPs. Keywords: LY294002, AKT, surfactant-free poly(lactic-co-glycolic acid), endoplasmic reticulum stressHou CCTsai TLSu WPHsieh HPYeh CSShieh DBSu WCDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2013, Iss default, Pp 2689-2707 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Hou CC Tsai TL Su WP Hsieh HP Yeh CS Shieh DB Su WC Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway
description	Chia-Cheng Hou,1,6 Tsung-Lin Tsai,1,6 Wen-Pin Su,6 Hsing-Pang Hsieh,7 Chen-Sheng Yeh,4,5 Dar-Bin Shieh,1–4 Wu-Chou Su1,6 1Institute of Basic Medical Sciences, 2Institute of Oral Medicine and Department of Stomatology, 3Advanced Optoelectronic Technology Center, 4Center for Micro/Nano Science and Technology, 5Department of Chemistry, 6Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan; 7Division of Biotechnology and Pharmaceutical Research, NHRI, Miaoli, Taiwan Background: LY294002 (LY) is a potent inhibitor of phosphatidylinositol 3-kinases (PI3Ks); however, biological applications of LY are limited by its poor solubility and pharmacokinetic profile. This study aimed at developing LY-loaded surfactant-free poly(lactic-co-glycolic acid) (PLGA) nanoparticles (SF-LY NPs) to improve the therapeutic efficacy of LY. Materials and methods: Cellular viability was measured by MTT assay. The subcellular distribution of NPs was studied using an ultraviolet-visible spectrophotometer and confocal microscope. The expression of cell-death-associated proteins was determined using Western blotting and the in vivo activity of SF-LY NPs was tested in a xenograft animal model. Results: SF-LY NPs enhanced the intracellular level of LY, induced sustained suppression of AKT, and induced marked cancer cell death. In addition, SF-LY NPs tended to accumulate in the endoplasmic reticulum (ER) and induce pronounced ER stress. Finally, SF-LY NPs exhibited a prominent antitumor effect in vivo. Conclusion: The surfactant-free formulation of PLGA is critical to the promising anticancer activity of SF-LY NPs. Keywords: LY294002, AKT, surfactant-free poly(lactic-co-glycolic acid), endoplasmic reticulum stress
format	article
author	Hou CC Tsai TL Su WP Hsieh HP Yeh CS Shieh DB Su WC
author_facet	Hou CC Tsai TL Su WP Hsieh HP Yeh CS Shieh DB Su WC
author_sort	Hou CC
title	Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway
title_short	Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway
title_full	Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway
title_fullStr	Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway
title_full_unstemmed	Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway
title_sort	pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the pi3k signaling pathway
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/f40d5c91f2a847a4b9d0a2f25a8c332a
work_keys_str_mv	AT houcc pronouncedinductionofendoplasmicreticulumstressandtumorsuppressionbysurfactantfreepolylacticcoglycolicacidnanoparticlesviamodulationofthepi3ksignalingpathway AT tsaitl pronouncedinductionofendoplasmicreticulumstressandtumorsuppressionbysurfactantfreepolylacticcoglycolicacidnanoparticlesviamodulationofthepi3ksignalingpathway AT suwp pronouncedinductionofendoplasmicreticulumstressandtumorsuppressionbysurfactantfreepolylacticcoglycolicacidnanoparticlesviamodulationofthepi3ksignalingpathway AT hsiehhp pronouncedinductionofendoplasmicreticulumstressandtumorsuppressionbysurfactantfreepolylacticcoglycolicacidnanoparticlesviamodulationofthepi3ksignalingpathway AT yehcs pronouncedinductionofendoplasmicreticulumstressandtumorsuppressionbysurfactantfreepolylacticcoglycolicacidnanoparticlesviamodulationofthepi3ksignalingpathway AT shiehdb pronouncedinductionofendoplasmicreticulumstressandtumorsuppressionbysurfactantfreepolylacticcoglycolicacidnanoparticlesviamodulationofthepi3ksignalingpathway AT suwc pronouncedinductionofendoplasmicreticulumstressandtumorsuppressionbysurfactantfreepolylacticcoglycolicacidnanoparticlesviamodulationofthepi3ksignalingpathway
_version_	1718404020681310208

Pronounced induction of endoplasmic reticulum stress and tumor suppression by surfactant-free poly (lactic-co-glycolic acid) nanoparticles via modulation of the PI3K signaling pathway

Ejemplares similares