Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer

Yue Gu,1,* Jing Li,2,* Yang Li,1 Lei Song,1 Dan Li,1 Liping Peng,1 Ying Wan,3 Shucheng Hua1 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Jilin University, Changchun, Jilin, 2Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Di...

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Autores principales:	Gu Y, Li J, Li Y, Song L, Li D, Peng LP, Wan Y, Hua SC
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	synergistic effect drug-resistance doxorubicin curcumin polymer micelles Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/a83b68cb1796450589a80c86d89b492c
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spelling	oai:doaj.org-article:a83b68cb1796450589a80c86d89b492c2021-12-02T03:11:31ZNanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer1178-2013https://doaj.org/article/a83b68cb1796450589a80c86d89b492c2016-11-01T00:00:00Zhttps://www.dovepress.com/nanomicelles-loaded-with-doxorubicin-and-curcumin-for-alleviating-mult-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yue Gu,1,* Jing Li,2,* Yang Li,1 Lei Song,1 Dan Li,1 Liping Peng,1 Ying Wan,3 Shucheng Hua1 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Jilin University, Changchun, Jilin, 2Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 3College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Purpose: A new type of polymeric micelle (PM) was assembled using a polyethylene glycol (PEG)-linked (PEGylated) amphiphilic copolymer and d-tocopheryl PEG1000 succinate (TPGS1000). The micelles were used to deliver doxorubicin (DOX) and curcumin (CUR) for alleviating multidrug resistance (MDR) in lung cancer cells while enhancing the therapeutic efficacy of DOX. Methods: Micelles loaded with DOX and CUR were assembled using a film-forming technique. Micelles were used to treat A549/Adr cells to find out whether micelles had the ability to reverse the MDR of A549/Adr cells. Some investigations were conducted using tumor-bearing mice to assess whether these micelles had enhanced antitumor efficacy as compared to DOX alone or the combination of DOX and CUR. Results: Some micelles (DOX + CUR)–PMs had a small average size of about 17 nm and showed definite ability to deliver both DOX and CUR into DOX-resistant A549/Adr cells. The PMs had high cytotoxicity toward A549/Adr cells when the applied equivalent DOX dose was 1 µg/mL or higher. The cellular uptake of (DOX + CUR)–PMs into A549/Adr cells was found to be associated with an energy-dependent, caveolae-mediated, and clathrin-independent mechanism. (DOX + CUR)–PMs helped to prolong the circulation of DOX or CUR as compared to the individual administration of DOX or CUR, and they exhibited high inhibiting efficiency against the growth of tumors and were able to reduce the side effects of DOX. Conclusion: TPGS1000 and CUR could synergistically reverse DOX-resistance of A549/Adr cells. In vivo examinations confirmed that the micelles had the capability to increase the plasma concentration of DOX or CUR, as well as to prolong their respective blood circulation. These micelles were able to significantly inhibit tumor growth in Lewis lung carcinoma tumor-bearing mice while reducing the side effects of DOX. The micelles showed potential in the treatment of lung cancer. Keywords: synergistic effect, drug-resistance, doxorubicin, curcumin, polymeric micellesGu YLi JLi YSong LLi DPeng LPWan YHua SCDove Medical Pressarticlesynergistic effectdrug-resistancedoxorubicincurcuminpolymer micellesMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 11, Pp 5757-5770 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	synergistic effect drug-resistance doxorubicin curcumin polymer micelles Medicine (General) R5-920
spellingShingle	synergistic effect drug-resistance doxorubicin curcumin polymer micelles Medicine (General) R5-920 Gu Y Li J Li Y Song L Li D Peng LP Wan Y Hua SC Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer
description	Yue Gu,1,* Jing Li,2,* Yang Li,1 Lei Song,1 Dan Li,1 Liping Peng,1 Ying Wan,3 Shucheng Hua1 1Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Jilin University, Changchun, Jilin, 2Hubei Province Key Laboratory on Cardiovascular, Cerebrovascular, and Metabolic Disorders, Hubei University of Science and Technology, Xianning, 3College of Life Sciences and Technology, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China *These authors contributed equally to this work Purpose: A new type of polymeric micelle (PM) was assembled using a polyethylene glycol (PEG)-linked (PEGylated) amphiphilic copolymer and d-tocopheryl PEG1000 succinate (TPGS1000). The micelles were used to deliver doxorubicin (DOX) and curcumin (CUR) for alleviating multidrug resistance (MDR) in lung cancer cells while enhancing the therapeutic efficacy of DOX. Methods: Micelles loaded with DOX and CUR were assembled using a film-forming technique. Micelles were used to treat A549/Adr cells to find out whether micelles had the ability to reverse the MDR of A549/Adr cells. Some investigations were conducted using tumor-bearing mice to assess whether these micelles had enhanced antitumor efficacy as compared to DOX alone or the combination of DOX and CUR. Results: Some micelles (DOX + CUR)–PMs had a small average size of about 17 nm and showed definite ability to deliver both DOX and CUR into DOX-resistant A549/Adr cells. The PMs had high cytotoxicity toward A549/Adr cells when the applied equivalent DOX dose was 1 µg/mL or higher. The cellular uptake of (DOX + CUR)–PMs into A549/Adr cells was found to be associated with an energy-dependent, caveolae-mediated, and clathrin-independent mechanism. (DOX + CUR)–PMs helped to prolong the circulation of DOX or CUR as compared to the individual administration of DOX or CUR, and they exhibited high inhibiting efficiency against the growth of tumors and were able to reduce the side effects of DOX. Conclusion: TPGS1000 and CUR could synergistically reverse DOX-resistance of A549/Adr cells. In vivo examinations confirmed that the micelles had the capability to increase the plasma concentration of DOX or CUR, as well as to prolong their respective blood circulation. These micelles were able to significantly inhibit tumor growth in Lewis lung carcinoma tumor-bearing mice while reducing the side effects of DOX. The micelles showed potential in the treatment of lung cancer. Keywords: synergistic effect, drug-resistance, doxorubicin, curcumin, polymeric micelles
format	article
author	Gu Y Li J Li Y Song L Li D Peng LP Wan Y Hua SC
author_facet	Gu Y Li J Li Y Song L Li D Peng LP Wan Y Hua SC
author_sort	Gu Y
title	Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer
title_short	Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer
title_full	Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer
title_fullStr	Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer
title_full_unstemmed	Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer
title_sort	nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/a83b68cb1796450589a80c86d89b492c
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Nanomicelles loaded with doxorubicin and curcumin for alleviating multidrug resistance in lung cancer

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