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Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway

BACKGROUND: Osteosarcoma is a malignant bone tumor with a high rate of lung metastasis and mortality. It has been demonstrated that resveratrol can inhibit tumor proliferation and metastasis, but its application is limited due to poor water solubility and low bioavailability. In this study, we propo...

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Autores principales: Zhu, Wen Ting, Zeng, Xiang Feng, Yang, Hua, Jia, Meng Lei, Zhang, Wei, Liu, Wei, Liu, Sheng Yao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204760/
https://www.ncbi.nlm.nih.gov/pubmed/37228445
http://dx.doi.org/10.2147/IJN.S398046
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author Zhu, Wen Ting
Zeng, Xiang Feng
Yang, Hua
Jia, Meng Lei
Zhang, Wei
Liu, Wei
Liu, Sheng Yao
author_facet Zhu, Wen Ting
Zeng, Xiang Feng
Yang, Hua
Jia, Meng Lei
Zhang, Wei
Liu, Wei
Liu, Sheng Yao
author_sort Zhu, Wen Ting
collection PubMed
description BACKGROUND: Osteosarcoma is a malignant bone tumor with a high rate of lung metastasis and mortality. It has been demonstrated that resveratrol can inhibit tumor proliferation and metastasis, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare folate-modified liposomes loaded with resveratrol to investigate its anti-osteosarcoma effect in vitro and in vivo. METHODS: We prepared and characterized resveratrol liposomes modified with folate (denoted as, FA-Res/Lps). The effects of FA-Res/Lps on human osteosarcoma cell 143B proliferation, apoptosis, and migration were investigated by MTT, cell cloning, wound-healing assay, transwell, and flow cytometry. A xenograft tumor and lung metastasis model of osteosarcoma was constructed to study the therapeutic effects of FA-Res/Lps on the growth and metastasis of osteosarcoma in vivo. RESULTS: The FA-Res/Lps were prepared with a particle size of 118.5 ± 0.71 and a small dispersion coefficient of 0.154 ± 0.005. We found that FA-modified liposomes significantly increased resveratrol uptake by osteosarcoma cells 143B in flow cytometric assay, resulting in FA-Res/Lps, which inhibit tumor proliferation, migration and induce apoptosis more effectively than free Res and Res/Lps. The mechanism of action may be associated with the inhibition of JAK2/STAT3 signaling. In vivo imaging demonstrated that FA-modified DiR-modified liposomes significantly increased the distribution of drugs at the tumor site, leading to significant inhibition of osteosarcoma growth and metastasis by FA-Res/Lps. Furthermore, we found that FA-Res/Lps did not cause any adverse effects on mice body weight, liver, or kidney tissues. CONCLUSION: Taken together, the anti-osteosarcoma effect of resveratrol is significantly enhanced when it is loaded into FA-modified liposomes. FA-Res/Lps is a promising strategy for the treatment of osteosarcoma.
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spelling pubmed-102047602023-05-24 Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway Zhu, Wen Ting Zeng, Xiang Feng Yang, Hua Jia, Meng Lei Zhang, Wei Liu, Wei Liu, Sheng Yao Int J Nanomedicine Original Research BACKGROUND: Osteosarcoma is a malignant bone tumor with a high rate of lung metastasis and mortality. It has been demonstrated that resveratrol can inhibit tumor proliferation and metastasis, but its application is limited due to poor water solubility and low bioavailability. In this study, we proposed to prepare folate-modified liposomes loaded with resveratrol to investigate its anti-osteosarcoma effect in vitro and in vivo. METHODS: We prepared and characterized resveratrol liposomes modified with folate (denoted as, FA-Res/Lps). The effects of FA-Res/Lps on human osteosarcoma cell 143B proliferation, apoptosis, and migration were investigated by MTT, cell cloning, wound-healing assay, transwell, and flow cytometry. A xenograft tumor and lung metastasis model of osteosarcoma was constructed to study the therapeutic effects of FA-Res/Lps on the growth and metastasis of osteosarcoma in vivo. RESULTS: The FA-Res/Lps were prepared with a particle size of 118.5 ± 0.71 and a small dispersion coefficient of 0.154 ± 0.005. We found that FA-modified liposomes significantly increased resveratrol uptake by osteosarcoma cells 143B in flow cytometric assay, resulting in FA-Res/Lps, which inhibit tumor proliferation, migration and induce apoptosis more effectively than free Res and Res/Lps. The mechanism of action may be associated with the inhibition of JAK2/STAT3 signaling. In vivo imaging demonstrated that FA-modified DiR-modified liposomes significantly increased the distribution of drugs at the tumor site, leading to significant inhibition of osteosarcoma growth and metastasis by FA-Res/Lps. Furthermore, we found that FA-Res/Lps did not cause any adverse effects on mice body weight, liver, or kidney tissues. CONCLUSION: Taken together, the anti-osteosarcoma effect of resveratrol is significantly enhanced when it is loaded into FA-modified liposomes. FA-Res/Lps is a promising strategy for the treatment of osteosarcoma. Dove 2023-05-19 /pmc/articles/PMC10204760/ /pubmed/37228445 http://dx.doi.org/10.2147/IJN.S398046 Text en © 2023 Zhu et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhu, Wen Ting
Zeng, Xiang Feng
Yang, Hua
Jia, Meng Lei
Zhang, Wei
Liu, Wei
Liu, Sheng Yao
Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway
title Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway
title_full Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway
title_fullStr Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway
title_full_unstemmed Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway
title_short Resveratrol Loaded by Folate-Modified Liposomes Inhibits Osteosarcoma Growth and Lung Metastasis via Regulating JAK2/STAT3 Pathway
title_sort resveratrol loaded by folate-modified liposomes inhibits osteosarcoma growth and lung metastasis via regulating jak2/stat3 pathway
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10204760/
https://www.ncbi.nlm.nih.gov/pubmed/37228445
http://dx.doi.org/10.2147/IJN.S398046
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