Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen
Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will no...
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MDPI AG
2020-07-01
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author | Munther Alomari Rabindran Jermy Balasamy Dana Almohazey Vijaya Ravinayagam Mohammad Al Hamad Deena Ababneh Hiba Bahmdan Abdul-Hakeem Alomari Zakaria Mokadem Abdelhamid Elaissari |
author_facet | Munther Alomari Rabindran Jermy Balasamy Dana Almohazey Vijaya Ravinayagam Mohammad Al Hamad Deena Ababneh Hiba Bahmdan Abdul-Hakeem Alomari Zakaria Mokadem Abdelhamid Elaissari |
author_sort | Munther Alomari |
collection | DOAJ |
description | Tamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery. |
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spelling | doaj.art-51b9fef1e252455d98ffef5b84806feb2023-11-20T06:10:10ZengMDPI AGPolymers2073-43602020-07-01127151610.3390/polym12071516Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to TamoxifenMunther Alomari0Rabindran Jermy Balasamy1Dana Almohazey2Vijaya Ravinayagam3Mohammad Al Hamad4Deena Ababneh5Hiba Bahmdan6Abdul-Hakeem Alomari7Zakaria Mokadem8Abdelhamid Elaissari9Department of Stem Cell Biology, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaDepartment of Nano-Medicine Research, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaDepartment of Stem Cell Biology, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaDeanship of Scientific Research, Department of Nano-Medicine Research, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaDepartment of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University, Post Box No. 1982, Dammam 31441, Saudi ArabiaDepartment of Basic Sciences and Humanities, College of Engineering, Imam Abdulrahman Bin Faisal University, Post Box No. 1982, Dammam 31441, Saudi ArabiaDepartment of Stem Cell Biology, Institute for Research and Medical Consultations, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaBiomedical Engineering Department, College of Engineering, Imam Abdulrahman Bin Faisal University, Dammam 31441, Saudi ArabiaApplied Organic Synthesis Laboratory-LSOA, University of Oran Es-Senia, Department of Chemistry, Bp 1524 El M’Naouer, Oran 31000, AlgeriaFrance Univ Lyon, University Claude Bernard Lyon-1, CNRS, LAGEP-UMR 5007, F-69622 Lyon, FranceTamoxifen (TAM) is a hormonal drug and is mainly used as an anti-estrogen in breast cancer patients. TAM binds to estrogen receptors (ERs), resulting in inhibition of estrogen signaling pathways and thus, a downregulation of cell proliferation. Cancer cells with negative or low ER expression will not uptake TAM and will show low response. Poly (methyl methacrylate) (PMMA) nanoparticles were prepared using surfactant-free emulsion polymerization, then were loaded with Nile red (NR), which resulted in PMMA-NR. To enhance TAM delivery to cervical cancer cells (HELA), which is considered ER-negative, we loaded TAM and polymethyl methacrylate nanoparticles-Nile-red into silica (PMMA-NR-Si-TAM). The uptake and intracellular distribution were visualized by confocal laser scanning microscopy, and the in vitro cytotoxic activity was evaluated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay using HELA and non-tumorigenic cell line HFF-1. The sensitivity of HELA (LC50: 207.31 µg/mL) and HFF-1 (LC50: 234.08 µg/mL) to free TAM was very low. However, after the encapsulation of TAM with PMMA-NR, the sensitivity significantly increased HELA (LC50: 71.83 µg/mL) and HFF-1 (LC50: 37.36 µg/mL). This indicates that TAM can be used for the treatment of ER-negative cervical cancer once conjugated to PMMA-NR nanoparticles. In addition, the PMMA-NR formulation appears to be highly suitable for cancer imaging and drug delivery.https://www.mdpi.com/2073-4360/12/7/1516Nile red (NR)PMMA-NR-Si-TAMTamoxifen (TAM)HELAcancerdelivery |
spellingShingle | Munther Alomari Rabindran Jermy Balasamy Dana Almohazey Vijaya Ravinayagam Mohammad Al Hamad Deena Ababneh Hiba Bahmdan Abdul-Hakeem Alomari Zakaria Mokadem Abdelhamid Elaissari Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen Polymers Nile red (NR) PMMA-NR-Si-TAM Tamoxifen (TAM) HELA cancer delivery |
title | Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen |
title_full | Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen |
title_fullStr | Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen |
title_full_unstemmed | Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen |
title_short | Nile Red-Poly(Methyl Methacrylate)/Silica Nanocomposite Particles Increase the Sensitivity of Cervical Cancer Cells to Tamoxifen |
title_sort | nile red poly methyl methacrylate silica nanocomposite particles increase the sensitivity of cervical cancer cells to tamoxifen |
topic | Nile red (NR) PMMA-NR-Si-TAM Tamoxifen (TAM) HELA cancer delivery |
url | https://www.mdpi.com/2073-4360/12/7/1516 |
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