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Co-Delivery of Ylang Ylang Oil of Cananga odorata 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 mea...
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| Huvudupphovsmän: | , , , , , , |
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| Materialtyp: | Artikel |
| Språk: | engelska |
| Publicerad: |
Philipps-Universität Marburg
2023
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| Länkar: | PDF-fulltext |
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| Sammanfattning: | 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 �g/mL)
when compared to Ox@NSs (0.006 �g/mL) and Y@NSs (18.39 �g/mL) or unloaded Ox (0.05 �g/mL)
and Y-oil (29.01 �g/mL). In addition, the percentages of theMDA-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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| Beskrivning: | Gefördert durch den Open-Access-Publikationsfonds der UB Marburg. |
| DOI: | 10.3390/ijms24098392 |