Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway

Jiao Wang,1 Rongrong Zhu,1 Xiaoyu Sun,1 Yanjing Zhu,1 Hui Liu,2 Shi-Long Wang1 1Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China; 2Eastern Hepatobiliary Surgery Hospital, Second Mil...

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Autores principales: Wang J, Zhu RR, Sun XY, Zhu YJ, Liu H, Wang SL
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Publicado: Dove Medical Press 2014
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spelling oai:doaj.org-article:5124be5c50c54faab5d60049b7ef7c832021-12-02T05:02:53ZIntracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway1178-2013https://doaj.org/article/5124be5c50c54faab5d60049b7ef7c832014-08-01T00:00:00Zhttp://www.dovepress.com/intracellular-uptake-of-etoposide-loaded-solid-lipid-nanoparticles-ind-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Jiao Wang,1 Rongrong Zhu,1 Xiaoyu Sun,1 Yanjing Zhu,1 Hui Liu,2 Shi-Long Wang1 1Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China; 2Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China Abstract: The objective of this study was to prepare and characterize etoposide (VP16)-loaded solid lipid nanoparticles (SLNs) and evaluate their antitumor activity in vitro. VP16-SLNs were prepared using emulsification and low-temperature solidification methods. The physicochemical properties of the VP16-SLNs were investigated by particle-size analysis, zeta potential measurement, drug loading, drug entrapment efficiency, stability, and in vitro drug-release behavior. In contrast to free VP16, the VP16-SLNs were well dispersed in aqueous medium, showing a narrow size distribution at 30–50 nm, a zeta potential value of −28.4 mV, high drug loading (36.91%), and an ideal drug entrapment efficiency (75.42%). The drug release of VP16-SLNs could last up to 60 hours and exhibited a sustained profile, which made it a promising vehicle for drug delivery. Furthermore, VP16-SLNs could significantly enhance in vitro cytotoxicity against SGC7901 cells compared to the free drug. Furthermore, VP16-SLNs could induce higher apoptotic rates, more significant cell cycle arrest effects, and greater cellular uptake in SGC7901 cells than free VP16. Moreover, results demonstrated that the mechanisms of VP16-SLNs were similar to those claimed for free VP16, including induction of cellular apoptosis by activation of p53, release of cytochrome c, loss of membrane potential, and activation of caspases. Thus, these results suggested that the SLNs might be a promising nanocarrier for VP16 to treat gastric carcinoma. Keywords: sustained profile, gastric carcinoma, SLNs, cytochrome c, caspasesWang JZhu RRSun XYZhu YJLiu HWang SLDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3987-3998 (2014)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Wang J
Zhu RR
Sun XY
Zhu YJ
Liu H
Wang SL
Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway
description Jiao Wang,1 Rongrong Zhu,1 Xiaoyu Sun,1 Yanjing Zhu,1 Hui Liu,2 Shi-Long Wang1 1Research Center for Translational Medicine at East Hospital, School of Life Science and Technology, Tongji University, Shanghai, People’s Republic of China; 2Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, People’s Republic of China Abstract: The objective of this study was to prepare and characterize etoposide (VP16)-loaded solid lipid nanoparticles (SLNs) and evaluate their antitumor activity in vitro. VP16-SLNs were prepared using emulsification and low-temperature solidification methods. The physicochemical properties of the VP16-SLNs were investigated by particle-size analysis, zeta potential measurement, drug loading, drug entrapment efficiency, stability, and in vitro drug-release behavior. In contrast to free VP16, the VP16-SLNs were well dispersed in aqueous medium, showing a narrow size distribution at 30–50 nm, a zeta potential value of −28.4 mV, high drug loading (36.91%), and an ideal drug entrapment efficiency (75.42%). The drug release of VP16-SLNs could last up to 60 hours and exhibited a sustained profile, which made it a promising vehicle for drug delivery. Furthermore, VP16-SLNs could significantly enhance in vitro cytotoxicity against SGC7901 cells compared to the free drug. Furthermore, VP16-SLNs could induce higher apoptotic rates, more significant cell cycle arrest effects, and greater cellular uptake in SGC7901 cells than free VP16. Moreover, results demonstrated that the mechanisms of VP16-SLNs were similar to those claimed for free VP16, including induction of cellular apoptosis by activation of p53, release of cytochrome c, loss of membrane potential, and activation of caspases. Thus, these results suggested that the SLNs might be a promising nanocarrier for VP16 to treat gastric carcinoma. Keywords: sustained profile, gastric carcinoma, SLNs, cytochrome c, caspases
format article
author Wang J
Zhu RR
Sun XY
Zhu YJ
Liu H
Wang SL
author_facet Wang J
Zhu RR
Sun XY
Zhu YJ
Liu H
Wang SL
author_sort Wang J
title Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway
title_short Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway
title_full Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway
title_fullStr Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway
title_full_unstemmed Intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway
title_sort intracellular uptake of etoposide-loaded solid lipid nanoparticles induces an enhancing inhibitory effect on gastric cancer through mitochondria-mediated apoptosis pathway
publisher Dove Medical Press
publishDate 2014
url https://doaj.org/article/5124be5c50c54faab5d60049b7ef7c83
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AT sunxy intracellularuptakeofetoposideloadedsolidlipidnanoparticlesinducesanenhancinginhibitoryeffectongastriccancerthroughmitochondriamediatedapoptosispathway
AT zhuyj intracellularuptakeofetoposideloadedsolidlipidnanoparticlesinducesanenhancinginhibitoryeffectongastriccancerthroughmitochondriamediatedapoptosispathway
AT liuh intracellularuptakeofetoposideloadedsolidlipidnanoparticlesinducesanenhancinginhibitoryeffectongastriccancerthroughmitochondriamediatedapoptosispathway
AT wangsl intracellularuptakeofetoposideloadedsolidlipidnanoparticlesinducesanenhancinginhibitoryeffectongastriccancerthroughmitochondriamediatedapoptosispathway
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