dc.contributor.author | Sedky, Nada K. | |
dc.contributor.author | Braoudaki, Maria | |
dc.contributor.author | Mahdy, Noha Khalil | |
dc.contributor.author | Amin, Kenzy | |
dc.contributor.author | Fawzy, Iten M. | |
dc.contributor.author | Efthimiadou, Eleni K. | |
dc.contributor.author | Youness, Rana A. | |
dc.contributor.author | Fahmy, Sherif Ashraf | |
dc.date.accessioned | 2023-09-27T20:15:00Z | |
dc.date.available | 2023-09-27T20:15:00Z | |
dc.date.issued | 2023-09-15 | |
dc.identifier.citation | Sedky , N K , Braoudaki , M , Mahdy , N K , Amin , K , Fawzy , I M , Efthimiadou , E K , Youness , R A & Fahmy , S A 2023 , ' Box–Behnken design of thermo-responsive nano-liposomes loaded with a platinum( iv ) anticancer complex: evaluation of cytotoxicity and apoptotic pathways in triple negative breast cancer cells † ' , Nanoscale Advances , vol. 5 , no. 19 , pp. 5399–5413 . https://doi.org/10.1039/d3na00368j | |
dc.identifier.other | Jisc: 1341075 | |
dc.identifier.other | publisher-id: d3na00368j | |
dc.identifier.uri | http://hdl.handle.net/2299/26777 | |
dc.description | © 2023 The Author(s). Published by the Royal Society of Chemistry. This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC), https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.description.abstract | Herein, thermo-responsive liposomes (TLs) loaded with Asp (Asp/TLs) were produced by self-assembling DPPC, DSPE-PEG2000, and cholesterol. The preparation variables were optimized using the Box–Behnken design (BBD). The optimized Asp/TLs exhibited an average particle size of 114.05 ± 1.56 nm, PDI of 0.15 ± 0.015, zeta potential of −15.24 ± 0.65 mV, and entrapment efficiency (EE%) of 84.08 ± 2.75%. In addition, under physiological conditions, Asp/TLs showed spherical shape, outstanding stability and thermo-triggered the release of Asp at 38 °C, reaching the maximum Asp release at 40 °C. The MTT assay showed that the optimal Asp/TLs exhibited the highest cytotoxic activity upon exposure to mild hyperthermia (40 °C) against the invasive triple-negative breast cancer cell line (MDA-MB-231) when compared to other preparations. The IC50 of Asp/TLs (40 °C) was estimated at 0.9 μg mL−1, while that of free Asp (40 °C) was 3.83 μg mL−1. As such, the optimal Asp/TLs were shown to increase the cytotoxic activity of Asp by 4-fold upon exposure to mild hyperthermia. The IC50 values of Asp and Asp/TLs without exposure to 40 °C were 6.6 μg mL−1 and 186 μg mL−1, respectively. This indicated that Asp was released only when placed at 40 °C. The apoptosis assay revealed that Asp/TLs (40 °C) caused a remarkable increase in the percentage of cell population among both the late apoptosis and necrosis quartiles, as well as a significant decline in the viable cell quartile (P ≤ 0.001) when compared to Asp (40 °C). Asp/TLs (40 °C) and Asp (40 °C) could stimulate the intrinsic apoptosis pathway by upregulating the apoptotic genes Bak and Bax, while downregulating the anti-apoptotic genes, BCL-xL and BCL-2. The free Asp (40 °C) increased the gene expression of Bak and Bax by 4.4- and 5.2-folds, while reducing the expression of BCL-xL and BCL-2 by 50% and 73%, respectively. The optimal Asp TLs (40 °C) manifested more potent effects as demonstrated by the upregulation of Bak, Bax, and P53 by 5.6-, 7.2-, and 1.3-folds, as well as the downregulation of BCL-xL and BCL-2 by 70% and 85%, respectively. As such, the optimal Asp TLs (40 °C) treatment displayed the most potent cytotoxic profile and induced both apoptosis and necrosis in MDA-MB-231. | en |
dc.format.extent | 15 | |
dc.format.extent | 3225255 | |
dc.language.iso | eng | |
dc.relation.ispartof | Nanoscale Advances | |
dc.title | Box–Behnken design of thermo-responsive nano-liposomes loaded with a platinum( iv ) anticancer complex: evaluation of cytotoxicity and apoptotic pathways in triple negative breast cancer cells † | en |
dc.contributor.institution | Centre for Future Societies Research | |
dc.contributor.institution | Department of Clinical, Pharmaceutical and Biological Science | |
dc.contributor.institution | School of Life and Medical Sciences | |
dc.contributor.institution | Biosciences Research Group | |
dc.contributor.institution | Centre for Research in Mechanisms of Disease and Drug Discovery | |
dc.description.status | Peer reviewed | |
dc.identifier.url | http://www.scopus.com/inward/record.url?scp=85172244059&partnerID=8YFLogxK | |
rioxxterms.versionofrecord | 10.1039/d3na00368j | |
rioxxterms.type | Journal Article/Review | |
herts.preservation.rarelyaccessed | true | |