Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer

Wen-Ting Zhu,1,2,* Sheng-Yao Liu,3,* Lei Wu,1,2 Hua-Li Xu,4 Jun Wang,1,2 Guo-Xin Ni,3,5 Qing-Bing Zeng1,2 1Biomaterial Research Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; 2Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceuti...

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Autores principales: Zhu WT, Liu SY, Wu L, Xu HL, Wang J, Ni GX, Zeng QB
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Publicado: Dove Medical Press 2017
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spelling oai:doaj.org-article:ab13d99f4c2e4cf28d8c2e7681da58e72021-12-02T05:10:44ZDelivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer1178-2013https://doaj.org/article/ab13d99f4c2e4cf28d8c2e7681da58e72017-04-01T00:00:00Zhttps://www.dovepress.com/delivery-of-curcumin-by-directed-self-assembled-micelles-enhances-ther-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Wen-Ting Zhu,1,2,* Sheng-Yao Liu,3,* Lei Wu,1,2 Hua-Li Xu,4 Jun Wang,1,2 Guo-Xin Ni,3,5 Qing-Bing Zeng1,2 1Biomaterial Research Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; 2Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; 3Department of Orthopeadics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 4Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; 5Department of Rehabilitation Medicine, First Affiliated Hospital, Fujian Medical University, Fuzhou, China *These authors contributed equally to this work Background: It has been widely reported that curcumin (CUR) exhibits anticancer activity and triggers the apoptosis of human A549 non-small-cell lung cancer (NSCLC) cells. However, its application is limited owing to its poor solubility and bioavailability. Therefore, there is an urgent need to develop a new CUR formulation with higher water solubility and better biocompatibility for clinical application in the future. Materials and methods: In this study, CUR-loaded methoxy polyethylene glycol–polylactide (CUR/mPEG–PLA) polymeric micelles were prepared by a thin-film hydration method. Their characteristics and antitumor effects were evaluated subsequently. Results: The average size of CUR/mPEG–PLA micelles was 34.9±2.1 nm with its polydispersity index (PDI) in the range of 0.067–0.168. The encapsulation efficiency and drug loading were 90.2%±0.78% and 9.1%±0.07%, respectively. CUR was constantly released from the CUR/mPEG–PLA micelles, and its cellular uptake in A549 cells was significantly increased. It was also found that CUR/mPEG–PLA micelles inhibited A549 cell proliferation, increased the cell cytotoxicity, induced G2/M stage arrest and promoted cell apoptosis. Moreover, the CUR/mPEG–PLA micelles suppressed the migration and invasion of A549 cells more obviously than free CUR. Additionally, CUR/mPEG–PLA micelles inhibited human umbilical vein endothelial cells migration, invasion and corresponding tube formation, implying the antiangiogenesis ability. Its enhanced antitumor mechanism may be related to the reduced expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, MMP-9 and Bcl-2 as well as the increased expression of Bax. Conclusion: The mPEG–PLA copolymer micelles can serve as an efficient carrier for CUR. The CUR/mPEG–PLA micelles have promising clinical potential in treating NSCLC. Keywords: curcumin, mPEG–PLA, polymeric micelles, A549 cells, HUVECs, angiogenesisZhu WTLiu SYWu LXu HLWang JNi GXZeng QBDove Medical PressarticleKeywords: CurcuminmPEG-PLAPolymeric micellesA549 cellsHUVECsAngiogenesisMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 2621-2634 (2017)
institution DOAJ
collection DOAJ
language EN
topic Keywords: Curcumin
mPEG-PLA
Polymeric micelles
A549 cells
HUVECs
Angiogenesis
Medicine (General)
R5-920
spellingShingle Keywords: Curcumin
mPEG-PLA
Polymeric micelles
A549 cells
HUVECs
Angiogenesis
Medicine (General)
R5-920
Zhu WT
Liu SY
Wu L
Xu HL
Wang J
Ni GX
Zeng QB
Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer
description Wen-Ting Zhu,1,2,* Sheng-Yao Liu,3,* Lei Wu,1,2 Hua-Li Xu,4 Jun Wang,1,2 Guo-Xin Ni,3,5 Qing-Bing Zeng1,2 1Biomaterial Research Center, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; 2Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; 3Department of Orthopeadics and Traumatology, Nanfang Hospital, Southern Medical University, Guangzhou, China; 4Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, China; 5Department of Rehabilitation Medicine, First Affiliated Hospital, Fujian Medical University, Fuzhou, China *These authors contributed equally to this work Background: It has been widely reported that curcumin (CUR) exhibits anticancer activity and triggers the apoptosis of human A549 non-small-cell lung cancer (NSCLC) cells. However, its application is limited owing to its poor solubility and bioavailability. Therefore, there is an urgent need to develop a new CUR formulation with higher water solubility and better biocompatibility for clinical application in the future. Materials and methods: In this study, CUR-loaded methoxy polyethylene glycol–polylactide (CUR/mPEG–PLA) polymeric micelles were prepared by a thin-film hydration method. Their characteristics and antitumor effects were evaluated subsequently. Results: The average size of CUR/mPEG–PLA micelles was 34.9±2.1 nm with its polydispersity index (PDI) in the range of 0.067–0.168. The encapsulation efficiency and drug loading were 90.2%±0.78% and 9.1%±0.07%, respectively. CUR was constantly released from the CUR/mPEG–PLA micelles, and its cellular uptake in A549 cells was significantly increased. It was also found that CUR/mPEG–PLA micelles inhibited A549 cell proliferation, increased the cell cytotoxicity, induced G2/M stage arrest and promoted cell apoptosis. Moreover, the CUR/mPEG–PLA micelles suppressed the migration and invasion of A549 cells more obviously than free CUR. Additionally, CUR/mPEG–PLA micelles inhibited human umbilical vein endothelial cells migration, invasion and corresponding tube formation, implying the antiangiogenesis ability. Its enhanced antitumor mechanism may be related to the reduced expression of vascular endothelial growth factor, matrix metalloproteinase (MMP)-2, MMP-9 and Bcl-2 as well as the increased expression of Bax. Conclusion: The mPEG–PLA copolymer micelles can serve as an efficient carrier for CUR. The CUR/mPEG–PLA micelles have promising clinical potential in treating NSCLC. Keywords: curcumin, mPEG–PLA, polymeric micelles, A549 cells, HUVECs, angiogenesis
format article
author Zhu WT
Liu SY
Wu L
Xu HL
Wang J
Ni GX
Zeng QB
author_facet Zhu WT
Liu SY
Wu L
Xu HL
Wang J
Ni GX
Zeng QB
author_sort Zhu WT
title Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer
title_short Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer
title_full Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer
title_fullStr Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer
title_full_unstemmed Delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer
title_sort delivery of curcumin by directed self-assembled micelles enhances therapeutic treatment of non-small-cell lung cancer
publisher Dove Medical Press
publishDate 2017
url https://doaj.org/article/ab13d99f4c2e4cf28d8c2e7681da58e7
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