Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation
Resistance to temozolomide (TMZ) is the main cause of death in glioblastoma multiforme (GBM). The use of nanocarriers for drug delivery applications is one of the known approaches to overcome drug resistance. This study aimed to investigate the possible effect of selenium–chitosan nanoparticles load...
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MDPI AG
2021-06-01
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| Series: | Nanomaterials |
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| author | Madineh Mazarei Pooria Mohammadi Arvejeh M. R. Mozafari Pegah Khosravian Sorayya Ghasemi |
| author_facet | Madineh Mazarei Pooria Mohammadi Arvejeh M. R. Mozafari Pegah Khosravian Sorayya Ghasemi |
| author_sort | Madineh Mazarei |
| collection | DOAJ |
| description | Resistance to temozolomide (TMZ) is the main cause of death in glioblastoma multiforme (GBM). The use of nanocarriers for drug delivery applications is one of the known approaches to overcome drug resistance. This study aimed to investigate the possible effect of selenium–chitosan nanoparticles loaded with TMZ on the efficacy of TMZ on the expression of MGMT, E2F6, and RELA genes and the rate of apoptosis in the C6 cell line. Selenium nanoparticles (SNPs) were loaded with TMZ and then they were coated by Eudragit<sup>®</sup> RS100 (Eud) and chitosan (C<sub>S</sub>) to prepare Se@TMZ/Eud-Cs. Physicochemical properties were determined by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDAX), thermal gravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) methods. Se@TMZ/Eud-Cs was evaluated for loading and release of TMZ by spectrophotometric method. Subsequently, SNPs loaded with curcumin (as a fluorophore) were analyzed for in vitro uptake by C6 cells. Cytotoxicity and apoptosis assay were measured by MTT assay and Annexin-PI methods. Finally, real-time PCR was utilized to determine the expression of MGMT, E2F6, and RELA genes. Se@TMZ/Eud-Cs was prepared with an average size of 200 nm as confirmed by the DLS and microscopical methods. Se@TMZ/Eud-Cs presented 82.77 ± 5.30 loading efficiency with slow and pH-sensitive release kinetics. SNPs loaded with curcumin showed a better uptake performance by C6 cells compared with free curcumin (<i>p</i>-value < 0.01). Coated nanoparticles loaded with TMZ showed higher cytotoxicity, apoptosis (<i>p</i>-value < 0.0001), and down-regulation of MGMT, E2F6, and RELA and lower IC50 value (<i>p</i>-value < 0.0001) than free TMZ and control (<i>p</i>-value < 0.0001) groups. Using Cs as a targeting agent in Se@TMZ/Eud-Cs system improved the possibility for targeted drug delivery to C6 cells. This drug delivery system enhanced the apoptosis rate and decreased the expression of genes related to TMZ resistance. In conclusion, Se@TMZ/Eud-Cs may be an option for the enhancement of TMZ efficiency in GBM treatment. |
| first_indexed | 2024-03-10T09:58:40Z |
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| last_indexed | 2024-03-10T09:58:40Z |
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| spelling | doaj.art-66a5ee668ddd401c9efa00bccba25e372023-11-22T02:06:08ZengMDPI AGNanomaterials2079-49912021-06-01117170410.3390/nano11071704Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene RegulationMadineh Mazarei0Pooria Mohammadi Arvejeh1M. R. Mozafari2Pegah Khosravian3Sorayya Ghasemi4Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord 88157-13471, IranCellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord 88157-13471, IranSupreme NanoBiotics Co. Ltd. and Supreme Pharmatech Co. Ltd., 399/90-95 Moo 13 Kingkaew Rd. Soi 25/1, T. Rachateva, A. Bangplee, Samutprakan 10540, ThailandMedical Plants Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord 88157-13471, IranCellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord 88157-13471, IranResistance to temozolomide (TMZ) is the main cause of death in glioblastoma multiforme (GBM). The use of nanocarriers for drug delivery applications is one of the known approaches to overcome drug resistance. This study aimed to investigate the possible effect of selenium–chitosan nanoparticles loaded with TMZ on the efficacy of TMZ on the expression of MGMT, E2F6, and RELA genes and the rate of apoptosis in the C6 cell line. Selenium nanoparticles (SNPs) were loaded with TMZ and then they were coated by Eudragit<sup>®</sup> RS100 (Eud) and chitosan (C<sub>S</sub>) to prepare Se@TMZ/Eud-Cs. Physicochemical properties were determined by scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDAX), thermal gravimetric analysis (TGA), Fourier-transform infrared spectroscopy (FTIR), and dynamic light scattering (DLS) methods. Se@TMZ/Eud-Cs was evaluated for loading and release of TMZ by spectrophotometric method. Subsequently, SNPs loaded with curcumin (as a fluorophore) were analyzed for in vitro uptake by C6 cells. Cytotoxicity and apoptosis assay were measured by MTT assay and Annexin-PI methods. Finally, real-time PCR was utilized to determine the expression of MGMT, E2F6, and RELA genes. Se@TMZ/Eud-Cs was prepared with an average size of 200 nm as confirmed by the DLS and microscopical methods. Se@TMZ/Eud-Cs presented 82.77 ± 5.30 loading efficiency with slow and pH-sensitive release kinetics. SNPs loaded with curcumin showed a better uptake performance by C6 cells compared with free curcumin (<i>p</i>-value < 0.01). Coated nanoparticles loaded with TMZ showed higher cytotoxicity, apoptosis (<i>p</i>-value < 0.0001), and down-regulation of MGMT, E2F6, and RELA and lower IC50 value (<i>p</i>-value < 0.0001) than free TMZ and control (<i>p</i>-value < 0.0001) groups. Using Cs as a targeting agent in Se@TMZ/Eud-Cs system improved the possibility for targeted drug delivery to C6 cells. This drug delivery system enhanced the apoptosis rate and decreased the expression of genes related to TMZ resistance. In conclusion, Se@TMZ/Eud-Cs may be an option for the enhancement of TMZ efficiency in GBM treatment.https://www.mdpi.com/2079-4991/11/7/1704glioblastoma multiformetemozolomideselenium nanoparticleCsEudRELA |
| spellingShingle | Madineh Mazarei Pooria Mohammadi Arvejeh M. R. Mozafari Pegah Khosravian Sorayya Ghasemi Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation Nanomaterials glioblastoma multiforme temozolomide selenium nanoparticle Cs Eud RELA |
| title | Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation |
| title_full | Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation |
| title_fullStr | Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation |
| title_full_unstemmed | Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation |
| title_short | Anticancer Potential of Temozolomide-Loaded Eudragit-Chitosan Coated Selenium Nanoparticles: In Vitro Evaluation of Cytotoxicity, Apoptosis and Gene Regulation |
| title_sort | anticancer potential of temozolomide loaded eudragit chitosan coated selenium nanoparticles in vitro evaluation of cytotoxicity apoptosis and gene regulation |
| topic | glioblastoma multiforme temozolomide selenium nanoparticle Cs Eud RELA |
| url | https://www.mdpi.com/2079-4991/11/7/1704 |
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