Enhancing ovarian cancer treatment: Synergistic effects of methotrexate (Methotrexate)- and quercetin-loaded chitosan nanoparticles

Ovarian cancer, a leading cause of cancer-related deaths in women, is often diagnosed at advanced stages and exhibits treatment resistance. This study investigates chitosan-based nanoparticles (Cs NPs) as a drug delivery system to enhance the efficacy of methotrexate (MTX) and quercetin (Que) in ova...

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Main Authors: Hamed Dadashi, Amir Reza Nazemiyeh, Alireza Karimian-Shaddel, Milad mashinchian, Aria Mohabbat, Shahrbano Karamnejad Faragheh, Somayeh Vandghanooni, Morteza Eskandani
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Carbohydrate Polymer Technologies and Applications
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666893924001993
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author Hamed Dadashi
Amir Reza Nazemiyeh
Alireza Karimian-Shaddel
Milad mashinchian
Aria Mohabbat
Shahrbano Karamnejad Faragheh
Somayeh Vandghanooni
Morteza Eskandani
author_facet Hamed Dadashi
Amir Reza Nazemiyeh
Alireza Karimian-Shaddel
Milad mashinchian
Aria Mohabbat
Shahrbano Karamnejad Faragheh
Somayeh Vandghanooni
Morteza Eskandani
author_sort Hamed Dadashi
collection DOAJ
description Ovarian cancer, a leading cause of cancer-related deaths in women, is often diagnosed at advanced stages and exhibits treatment resistance. This study investigates chitosan-based nanoparticles (Cs NPs) as a drug delivery system to enhance the efficacy of methotrexate (MTX) and quercetin (Que) in ovarian cancer therapy. Cs NPs were synthesized for drug delivery, and their physicochemical properties, in vitro release profiles, and cytotoxicity against OVCAR-3 cells were evaluated. The study found high encapsulation efficiencies of 97.92 % for MTX and 76.23 % for Que, with controlled release demonstrated at pH 5.7 over 50 h. Cytotoxicity assays revealed IC50 values of 57.23 ng/mL for MTX-Cs NPs and 13.22 ng/mL for Que-Cs NPs, indicating superior effectiveness compared to plain drugs. The combination treatment showed a synergistic effect (CI of 0.266), significantly enhancing apoptosis and reducing OVCAR-3 mammosphere size by 25 %. Cell migration assays indicated a reduction to 25.02 % compared to controls. The CAM assay confirmed anti-angiogenic activity, while Western blot analysis showed reduced E2F-1 and increased BAX expression. These findings suggest that MTX/Que-loaded Cs NPs could significantly improve ovarian cancer treatment outcomes.
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institution Kabale University
issn 2666-8939
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publishDate 2024-12-01
publisher Elsevier
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series Carbohydrate Polymer Technologies and Applications
spelling doaj-art-02be4d85f36d46c499f230528f1aade42024-12-13T11:06:39ZengElsevierCarbohydrate Polymer Technologies and Applications2666-89392024-12-018100619Enhancing ovarian cancer treatment: Synergistic effects of methotrexate (Methotrexate)- and quercetin-loaded chitosan nanoparticlesHamed Dadashi0Amir Reza Nazemiyeh1Alireza Karimian-Shaddel2Milad mashinchian3Aria Mohabbat4Shahrbano Karamnejad Faragheh5Somayeh Vandghanooni6Morteza Eskandani7Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, IranResearch Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, IranResearch Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, IranResearch Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, IranResearch Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, IranResearch Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, IranHematology and Oncology Research Center, Tabriz university of Medical Sciences, Tabriz, Iran; Corresponding author at: Hematology and Oncology Research Center, Tabriz university of Medical Sciences, Tabriz, Iran.Research Center for Pharmaceutical Nanotechnology, Biomedicine Institute, Tabriz University of Medical Sciences, Tabriz, Iran; Corresponding author at: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.Ovarian cancer, a leading cause of cancer-related deaths in women, is often diagnosed at advanced stages and exhibits treatment resistance. This study investigates chitosan-based nanoparticles (Cs NPs) as a drug delivery system to enhance the efficacy of methotrexate (MTX) and quercetin (Que) in ovarian cancer therapy. Cs NPs were synthesized for drug delivery, and their physicochemical properties, in vitro release profiles, and cytotoxicity against OVCAR-3 cells were evaluated. The study found high encapsulation efficiencies of 97.92 % for MTX and 76.23 % for Que, with controlled release demonstrated at pH 5.7 over 50 h. Cytotoxicity assays revealed IC50 values of 57.23 ng/mL for MTX-Cs NPs and 13.22 ng/mL for Que-Cs NPs, indicating superior effectiveness compared to plain drugs. The combination treatment showed a synergistic effect (CI of 0.266), significantly enhancing apoptosis and reducing OVCAR-3 mammosphere size by 25 %. Cell migration assays indicated a reduction to 25.02 % compared to controls. The CAM assay confirmed anti-angiogenic activity, while Western blot analysis showed reduced E2F-1 and increased BAX expression. These findings suggest that MTX/Que-loaded Cs NPs could significantly improve ovarian cancer treatment outcomes.http://www.sciencedirect.com/science/article/pii/S2666893924001993Ovarian neoplasmsMethotrexate (Methotrexate)QuercetinChitosan nanoparticlesDrug delivery systemsAntineoplastic agents
spellingShingle Hamed Dadashi
Amir Reza Nazemiyeh
Alireza Karimian-Shaddel
Milad mashinchian
Aria Mohabbat
Shahrbano Karamnejad Faragheh
Somayeh Vandghanooni
Morteza Eskandani
Enhancing ovarian cancer treatment: Synergistic effects of methotrexate (Methotrexate)- and quercetin-loaded chitosan nanoparticles
Carbohydrate Polymer Technologies and Applications
Ovarian neoplasms
Methotrexate (Methotrexate)
Quercetin
Chitosan nanoparticles
Drug delivery systems
Antineoplastic agents
title Enhancing ovarian cancer treatment: Synergistic effects of methotrexate (Methotrexate)- and quercetin-loaded chitosan nanoparticles
title_full Enhancing ovarian cancer treatment: Synergistic effects of methotrexate (Methotrexate)- and quercetin-loaded chitosan nanoparticles
title_fullStr Enhancing ovarian cancer treatment: Synergistic effects of methotrexate (Methotrexate)- and quercetin-loaded chitosan nanoparticles
title_full_unstemmed Enhancing ovarian cancer treatment: Synergistic effects of methotrexate (Methotrexate)- and quercetin-loaded chitosan nanoparticles
title_short Enhancing ovarian cancer treatment: Synergistic effects of methotrexate (Methotrexate)- and quercetin-loaded chitosan nanoparticles
title_sort enhancing ovarian cancer treatment synergistic effects of methotrexate methotrexate and quercetin loaded chitosan nanoparticles
topic Ovarian neoplasms
Methotrexate (Methotrexate)
Quercetin
Chitosan nanoparticles
Drug delivery systems
Antineoplastic agents
url http://www.sciencedirect.com/science/article/pii/S2666893924001993
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