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Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy
BACKGROUND: Baicalin (BAN) has attracted widespread attention due to its low-toxicity and efficient antitumor activity, but its poor water solubility and low bioavailability severely limit its clinical application. Development of a targeted drug delivery system is a good strategy to improve the anti...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove
2021
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714011/ https://www.ncbi.nlm.nih.gov/pubmed/34992370 http://dx.doi.org/10.2147/IJN.S340764 |
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author | Mi, Xiao Hu, Meigeng Dong, Mingran Yang, Zhihong Zhan, Xia Chang, Xinyue Lu, Juan Chen, Xi |
author_facet | Mi, Xiao Hu, Meigeng Dong, Mingran Yang, Zhihong Zhan, Xia Chang, Xinyue Lu, Juan Chen, Xi |
author_sort | Mi, Xiao |
collection | PubMed |
description | BACKGROUND: Baicalin (BAN) has attracted widespread attention due to its low-toxicity and efficient antitumor activity, but its poor water solubility and low bioavailability severely limit its clinical application. Development of a targeted drug delivery system is a good strategy to improve the antitumor activity of baicalin. METHODS: We prepared a BAN nano-drug delivery system PEG-FA@ZIF-8@BAN with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR). We characterized this system in terms of morphology, particle size, zeta-potential, infrared (IR), ultraviolet (UV), x-ray diffraction (XRD), and Brunel-Emmett-Teller (BET), and examined the in vitro cytotoxicity and cellular uptake properties of PEG-FA@ZIF-8@BAN using MCF-7 cells. Lastly, we established a 4T1 tumor-bearing mouse model and evaluated its in vivo anti-mammary cancer activity. RESULTS: The PEG-FA@ZIF-8@BAN nano-delivery system had good dispersion with a BAN loading efficiency of 41.45 ± 1.43%, hydrated particle size of 176 ± 8.1 nm, Zeta-potential of −23.83 ± 1.1 mV, and slow and massive drug release in an acidic environment (pH 5.0), whereas release was 11.03% in a neutral environment (pH 7.4). In vitro studies showed that PEG-FA@ZIF-8@BAN could significantly enhance the killing effect of BAN on MCF-7 cells, and the folic acid-mediated targeting could lead to better uptake of nanoparticles by tumor cells and thus better killing of cancer cells. In vivo studies also showed that PEG-FA@ZIF-8@BAN significantly increased the inhibition of the proliferation of solid breast cancer tumors (p < 0.01 or p < 0.001). CONCLUSION: The PEG-FA@ZIF-8@BAN nano-drug delivery system significantly enhanced the anti-breast cancer effect of baicalin both in vivo and in vitro, providing a more promising drug delivery system for the clinical applications and tumor management. |
format | Online Article Text |
id | pubmed-8714011 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Dove |
record_format | MEDLINE/PubMed |
spelling | pubmed-87140112022-01-05 Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy Mi, Xiao Hu, Meigeng Dong, Mingran Yang, Zhihong Zhan, Xia Chang, Xinyue Lu, Juan Chen, Xi Int J Nanomedicine Original Research BACKGROUND: Baicalin (BAN) has attracted widespread attention due to its low-toxicity and efficient antitumor activity, but its poor water solubility and low bioavailability severely limit its clinical application. Development of a targeted drug delivery system is a good strategy to improve the antitumor activity of baicalin. METHODS: We prepared a BAN nano-drug delivery system PEG-FA@ZIF-8@BAN with a zeolite imidazole framework-8 (ZIF-8) as a carrier, which can achieve the response of folate receptor (FR). We characterized this system in terms of morphology, particle size, zeta-potential, infrared (IR), ultraviolet (UV), x-ray diffraction (XRD), and Brunel-Emmett-Teller (BET), and examined the in vitro cytotoxicity and cellular uptake properties of PEG-FA@ZIF-8@BAN using MCF-7 cells. Lastly, we established a 4T1 tumor-bearing mouse model and evaluated its in vivo anti-mammary cancer activity. RESULTS: The PEG-FA@ZIF-8@BAN nano-delivery system had good dispersion with a BAN loading efficiency of 41.45 ± 1.43%, hydrated particle size of 176 ± 8.1 nm, Zeta-potential of −23.83 ± 1.1 mV, and slow and massive drug release in an acidic environment (pH 5.0), whereas release was 11.03% in a neutral environment (pH 7.4). In vitro studies showed that PEG-FA@ZIF-8@BAN could significantly enhance the killing effect of BAN on MCF-7 cells, and the folic acid-mediated targeting could lead to better uptake of nanoparticles by tumor cells and thus better killing of cancer cells. In vivo studies also showed that PEG-FA@ZIF-8@BAN significantly increased the inhibition of the proliferation of solid breast cancer tumors (p < 0.01 or p < 0.001). CONCLUSION: The PEG-FA@ZIF-8@BAN nano-drug delivery system significantly enhanced the anti-breast cancer effect of baicalin both in vivo and in vitro, providing a more promising drug delivery system for the clinical applications and tumor management. Dove 2021-12-24 /pmc/articles/PMC8714011/ /pubmed/34992370 http://dx.doi.org/10.2147/IJN.S340764 Text en © 2021 Mi 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 Mi, Xiao Hu, Meigeng Dong, Mingran Yang, Zhihong Zhan, Xia Chang, Xinyue Lu, Juan Chen, Xi Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy |
title | Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy |
title_full | Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy |
title_fullStr | Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy |
title_full_unstemmed | Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy |
title_short | Folic Acid Decorated Zeolitic Imidazolate Framework (ZIF-8) Loaded with Baicalin as a Nano-Drug Delivery System for Breast Cancer Therapy |
title_sort | folic acid decorated zeolitic imidazolate framework (zif-8) loaded with baicalin as a nano-drug delivery system for breast cancer therapy |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8714011/ https://www.ncbi.nlm.nih.gov/pubmed/34992370 http://dx.doi.org/10.2147/IJN.S340764 |
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