Co-Delivery of Ylang Ylang Oil of <i>Cananga odorata</i> and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer
Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean p...
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MDPI AG
2023-05-01
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| Series: | International Journal of Molecular Sciences |
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| author | Nada K. Sedky Nour M. Abdel-Kader Marwa Y. Issa Manal M. M. Abdelhady Samir N. Shamma Udo Bakowsky Sherif Ashraf Fahmy |
| author_facet | Nada K. Sedky Nour M. Abdel-Kader Marwa Y. Issa Manal M. M. Abdelhady Samir N. Shamma Udo Bakowsky Sherif Ashraf Fahmy |
| author_sort | Nada K. Sedky |
| collection | DOAJ |
| description | Smart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes’ cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 µg/mL) when compared to Ox@NSs (0.006 µg/mL) and Y@NSs (18.39 µg/mL) or unloaded Ox (0.05 µg/mL) and Y-oil (29.01 µg/mL)<b>.</b> In addition, the percentages of the MDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy. |
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| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T04:16:10Z |
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| spelling | doaj.art-65b4fc7bbbeb4d8cbc0c0fe83c9078892023-11-17T23:09:02ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-05-01249839210.3390/ijms24098392Co-Delivery of Ylang Ylang Oil of <i>Cananga odorata</i> and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast CancerNada K. Sedky0Nour M. Abdel-Kader1Marwa Y. Issa2Manal M. M. Abdelhady3Samir N. Shamma4Udo Bakowsky5Sherif Ashraf Fahmy6Department of Biochemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, EgyptDepartment of Biochemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, EgyptDepartment of Pharmacognosy, Faculty of Pharmacy, Cairo University, Kasr El-Aini Street, Cairo 11562, EgyptClinical Pharmacy Department, Faculty of Pharmacy, Badr University, Cairo 11829, EgyptInstitute of Global Health and Human Ecology, School of Sciences & Engineering, The American University in Cairo, AUC Avenue, P.O. Box 74, New Cairo 11835, EgyptDepartment of Pharmaceutics and Biopharmaceutics, University of Marburg, Robert-Koch-Str. 4, 35037 Marburg, GermanyDepartment of Chemistry, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, R5 New Garden City, New Administrative Capital, Cairo 11835, EgyptSmart pH-responsive niosomes loaded with either Oxaliplatin (Ox), Ylang ylang essential oil (Y-oil), or co-loaded with both compounds (Ox-Y) (Ox@NSs, Y@NSs, and Ox-Y@NSs, respectively) were formulated utilizing the thin film method. The developed nanocontainers had a spherical morphology with mean particle sizes lower than 170 nm and showed negative surface charges, high entrapment efficiencies, and a pH-dependent release over 24 h. The prepared pH-responsive niosomes’ cytotoxicity was tested against the invasive triple-negative breast cancer (MDA-MB-231) cells, compared to free OX and Y-oil. All niosomal formulations loaded with Ox and/or Y-oil significantly improved cytotoxic activity relative to their free counterparts. The Ox-Y@NSs demonstrated the lowest IC50 (0.0002 µg/mL) when compared to Ox@NSs (0.006 µg/mL) and Y@NSs (18.39 µg/mL) or unloaded Ox (0.05 µg/mL) and Y-oil (29.01 µg/mL)<b>.</b> In addition, the percentages of the MDA-MB-231 cell population in the late apoptotic and necrotic quartiles were profoundly higher in cells treated with the smart Ox-Y@NSs (8.38% and 5.06%) than those exposed to free Ox (7.33% and 1.93%) or Y-oil (2.3% and 2.13%) treatments. Gene expression analysis and protein assays were performed to provide extra elucidation regarding the molecular mechanism by which the prepared pH-sensitive niosomes induce apoptosis. Ox-Y@NSs significantly induced the gene expression of the apoptotic markers Tp53, Bax, and Caspase-7, while downregulating the antiapoptotic Bcl2. As such, Ox-Y@NSs are shown to activate the intrinsic pathway of apoptosis. Moreover, the protein assay ascertained the apoptotic effects of Ox-Y@NSs, generating a 4-fold increase in the relative protein quantity of the late apoptotic marker Caspase-7. Our findings suggest that combining natural essential oil with synthetic platinum-based drugs in pH-responsive nanovesicles is a promising approach to breast cancer therapy.https://www.mdpi.com/1422-0067/24/9/8392essential oilsplatinum-based anticancer drugsoxaliplatinniosomescytotoxicityinvasive breast cancer |
| spellingShingle | Nada K. Sedky Nour M. Abdel-Kader Marwa Y. Issa Manal M. M. Abdelhady Samir N. Shamma Udo Bakowsky Sherif Ashraf Fahmy Co-Delivery of Ylang Ylang Oil of <i>Cananga odorata</i> and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer International Journal of Molecular Sciences essential oils platinum-based anticancer drugs oxaliplatin niosomes cytotoxicity invasive breast cancer |
| title | Co-Delivery of Ylang Ylang Oil of <i>Cananga odorata</i> and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer |
| title_full | Co-Delivery of Ylang Ylang Oil of <i>Cananga odorata</i> and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer |
| title_fullStr | Co-Delivery of Ylang Ylang Oil of <i>Cananga odorata</i> and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer |
| title_full_unstemmed | Co-Delivery of Ylang Ylang Oil of <i>Cananga odorata</i> and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer |
| title_short | Co-Delivery of Ylang Ylang Oil of <i>Cananga odorata</i> and Oxaliplatin Using Intelligent pH-Sensitive Lipid-Based Nanovesicles for the Effective Treatment of Triple-Negative Breast Cancer |
| title_sort | co delivery of ylang ylang oil of i cananga odorata i and oxaliplatin using intelligent ph sensitive lipid based nanovesicles for the effective treatment of triple negative breast cancer |
| topic | essential oils platinum-based anticancer drugs oxaliplatin niosomes cytotoxicity invasive breast cancer |
| url | https://www.mdpi.com/1422-0067/24/9/8392 |
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