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...

Full description

Bibliographic Details
Main Authors: Munther Alomari, Rabindran Jermy Balasamy, Dana Almohazey, Vijaya Ravinayagam, Mohammad Al Hamad, Deena Ababneh, Hiba Bahmdan, Abdul-Hakeem Alomari, Zakaria Mokadem, Abdelhamid Elaissari
Format: Article
Language:English
Published: MDPI AG 2020-07-01
Series:Polymers
Subjects:
Online Access:https://www.mdpi.com/2073-4360/12/7/1516
_version_ 1797563008880214016
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.
first_indexed 2024-03-10T18:36:29Z
format Article
id doaj.art-51b9fef1e252455d98ffef5b84806feb
institution Directory Open Access Journal
issn 2073-4360
language English
last_indexed 2024-03-10T18:36:29Z
publishDate 2020-07-01
publisher MDPI AG
record_format Article
series Polymers
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
work_keys_str_mv AT muntheralomari nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT rabindranjermybalasamy nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT danaalmohazey nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT vijayaravinayagam nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT mohammadalhamad nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT deenaababneh nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT hibabahmdan nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT abdulhakeemalomari nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT zakariamokadem nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen
AT abdelhamidelaissari nileredpolymethylmethacrylatesilicananocompositeparticlesincreasethesensitivityofcervicalcancercellstotamoxifen