A novel approach for the co-delivery of 5-fluorouracil and everolimus for breast cancer combination therapy: stimuli-responsive chitosan hydrogel embedded with mesoporous silica nanoparticles
Background Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy...
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| Vydané v: | Journal of translational medicine Ročník 23; číslo 1; s. 382 - 18 |
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| Hlavní autori: | , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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London
BioMed Central
31.03.2025
BioMed Central Ltd BMC |
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| ISSN: | 1479-5876, 1479-5876 |
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| Abstract | Background
Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy by targeting multiple pathways in cancer progression. In this study, we developed an injectable, stimuli-responsive nanosystem using a chitosan hydrogel embedded with mesoporous silica nanoparticles for the co-administration of 5-fluorouracil and everolimus. This approach aims to optimize controlled drug release, enhance the synergistic anticancer effect, and overcome challenges associated with co-loading different therapeutic agents.
Methods
Various techniques were employed to characterize the nanoparticles and the hydrogel. Cell uptake, apoptosis, and proliferation of 4T1 breast cancer cells were evaluated by flow cytometry and Resazurin assay, respectively. The Balb/C mice model of breast cancer, which received the therapeutical nanoplatforms subcutaneously near the tumoral region was used to examine tumor size and lung metastases.
Results
The results revealed that the nanoparticles had a suitable loading capacity and high cellular uptake. The drug release was pH-sensitive and synergistic. By incorporating nanoparticles into the hydrogel, the cell death rate and apoptosis of 4T1 breast cancer cells increased significantly, due to the synergistic effects of co-delivered drugs. Additionally, the combination treatment groups showed a significant reduction in tumor size and lung metastasis compared to the monotherapy and control groups.
Conclusions
These findings underscore the potential of the nanocomposite used to develop a novel co-delivery system to enhance therapeutic outcomes, reduce side effects, and provide a promising new strategy for future cancer treatments. |
|---|---|
| AbstractList | Background
Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy by targeting multiple pathways in cancer progression. In this study, we developed an injectable, stimuli-responsive nanosystem using a chitosan hydrogel embedded with mesoporous silica nanoparticles for the co-administration of 5-fluorouracil and everolimus. This approach aims to optimize controlled drug release, enhance the synergistic anticancer effect, and overcome challenges associated with co-loading different therapeutic agents.
Methods
Various techniques were employed to characterize the nanoparticles and the hydrogel. Cell uptake, apoptosis, and proliferation of 4T1 breast cancer cells were evaluated by flow cytometry and Resazurin assay, respectively. The Balb/C mice model of breast cancer, which received the therapeutical nanoplatforms subcutaneously near the tumoral region was used to examine tumor size and lung metastases.
Results
The results revealed that the nanoparticles had a suitable loading capacity and high cellular uptake. The drug release was pH-sensitive and synergistic. By incorporating nanoparticles into the hydrogel, the cell death rate and apoptosis of 4T1 breast cancer cells increased significantly, due to the synergistic effects of co-delivered drugs. Additionally, the combination treatment groups showed a significant reduction in tumor size and lung metastasis compared to the monotherapy and control groups.
Conclusions
These findings underscore the potential of the nanocomposite used to develop a novel co-delivery system to enhance therapeutic outcomes, reduce side effects, and provide a promising new strategy for future cancer treatments. Background Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy by targeting multiple pathways in cancer progression. In this study, we developed an injectable, stimuli-responsive nanosystem using a chitosan hydrogel embedded with mesoporous silica nanoparticles for the co-administration of 5-fluorouracil and everolimus. This approach aims to optimize controlled drug release, enhance the synergistic anticancer effect, and overcome challenges associated with co-loading different therapeutic agents. Methods Various techniques were employed to characterize the nanoparticles and the hydrogel. Cell uptake, apoptosis, and proliferation of 4T1 breast cancer cells were evaluated by flow cytometry and Resazurin assay, respectively. The Balb/C mice model of breast cancer, which received the therapeutical nanoplatforms subcutaneously near the tumoral region was used to examine tumor size and lung metastases. Results The results revealed that the nanoparticles had a suitable loading capacity and high cellular uptake. The drug release was pH-sensitive and synergistic. By incorporating nanoparticles into the hydrogel, the cell death rate and apoptosis of 4T1 breast cancer cells increased significantly, due to the synergistic effects of co-delivered drugs. Additionally, the combination treatment groups showed a significant reduction in tumor size and lung metastasis compared to the monotherapy and control groups. Conclusions These findings underscore the potential of the nanocomposite used to develop a novel co-delivery system to enhance therapeutic outcomes, reduce side effects, and provide a promising new strategy for future cancer treatments. Keywords: Drug delivery, Nanocomposite, Mesopores, Hydrogels, Synergism, Breast neoplasm Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy by targeting multiple pathways in cancer progression. In this study, we developed an injectable, stimuli-responsive nanosystem using a chitosan hydrogel embedded with mesoporous silica nanoparticles for the co-administration of 5-fluorouracil and everolimus. This approach aims to optimize controlled drug release, enhance the synergistic anticancer effect, and overcome challenges associated with co-loading different therapeutic agents. Various techniques were employed to characterize the nanoparticles and the hydrogel. Cell uptake, apoptosis, and proliferation of 4T1 breast cancer cells were evaluated by flow cytometry and Resazurin assay, respectively. The Balb/C mice model of breast cancer, which received the therapeutical nanoplatforms subcutaneously near the tumoral region was used to examine tumor size and lung metastases. The results revealed that the nanoparticles had a suitable loading capacity and high cellular uptake. The drug release was pH-sensitive and synergistic. By incorporating nanoparticles into the hydrogel, the cell death rate and apoptosis of 4T1 breast cancer cells increased significantly, due to the synergistic effects of co-delivered drugs. Additionally, the combination treatment groups showed a significant reduction in tumor size and lung metastasis compared to the monotherapy and control groups. These findings underscore the potential of the nanocomposite used to develop a novel co-delivery system to enhance therapeutic outcomes, reduce side effects, and provide a promising new strategy for future cancer treatments. Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy by targeting multiple pathways in cancer progression. In this study, we developed an injectable, stimuli-responsive nanosystem using a chitosan hydrogel embedded with mesoporous silica nanoparticles for the co-administration of 5-fluorouracil and everolimus. This approach aims to optimize controlled drug release, enhance the synergistic anticancer effect, and overcome challenges associated with co-loading different therapeutic agents.BACKGROUNDBreast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy by targeting multiple pathways in cancer progression. In this study, we developed an injectable, stimuli-responsive nanosystem using a chitosan hydrogel embedded with mesoporous silica nanoparticles for the co-administration of 5-fluorouracil and everolimus. This approach aims to optimize controlled drug release, enhance the synergistic anticancer effect, and overcome challenges associated with co-loading different therapeutic agents.Various techniques were employed to characterize the nanoparticles and the hydrogel. Cell uptake, apoptosis, and proliferation of 4T1 breast cancer cells were evaluated by flow cytometry and Resazurin assay, respectively. The Balb/C mice model of breast cancer, which received the therapeutical nanoplatforms subcutaneously near the tumoral region was used to examine tumor size and lung metastases.METHODSVarious techniques were employed to characterize the nanoparticles and the hydrogel. Cell uptake, apoptosis, and proliferation of 4T1 breast cancer cells were evaluated by flow cytometry and Resazurin assay, respectively. The Balb/C mice model of breast cancer, which received the therapeutical nanoplatforms subcutaneously near the tumoral region was used to examine tumor size and lung metastases.The results revealed that the nanoparticles had a suitable loading capacity and high cellular uptake. The drug release was pH-sensitive and synergistic. By incorporating nanoparticles into the hydrogel, the cell death rate and apoptosis of 4T1 breast cancer cells increased significantly, due to the synergistic effects of co-delivered drugs. Additionally, the combination treatment groups showed a significant reduction in tumor size and lung metastasis compared to the monotherapy and control groups.RESULTSThe results revealed that the nanoparticles had a suitable loading capacity and high cellular uptake. The drug release was pH-sensitive and synergistic. By incorporating nanoparticles into the hydrogel, the cell death rate and apoptosis of 4T1 breast cancer cells increased significantly, due to the synergistic effects of co-delivered drugs. Additionally, the combination treatment groups showed a significant reduction in tumor size and lung metastasis compared to the monotherapy and control groups.These findings underscore the potential of the nanocomposite used to develop a novel co-delivery system to enhance therapeutic outcomes, reduce side effects, and provide a promising new strategy for future cancer treatments.CONCLUSIONSThese findings underscore the potential of the nanocomposite used to develop a novel co-delivery system to enhance therapeutic outcomes, reduce side effects, and provide a promising new strategy for future cancer treatments. Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy by targeting multiple pathways in cancer progression. In this study, we developed an injectable, stimuli-responsive nanosystem using a chitosan hydrogel embedded with mesoporous silica nanoparticles for the co-administration of 5-fluorouracil and everolimus. This approach aims to optimize controlled drug release, enhance the synergistic anticancer effect, and overcome challenges associated with co-loading different therapeutic agents. Various techniques were employed to characterize the nanoparticles and the hydrogel. Cell uptake, apoptosis, and proliferation of 4T1 breast cancer cells were evaluated by flow cytometry and Resazurin assay, respectively. The Balb/C mice model of breast cancer, which received the therapeutical nanoplatforms subcutaneously near the tumoral region was used to examine tumor size and lung metastases. The results revealed that the nanoparticles had a suitable loading capacity and high cellular uptake. The drug release was pH-sensitive and synergistic. By incorporating nanoparticles into the hydrogel, the cell death rate and apoptosis of 4T1 breast cancer cells increased significantly, due to the synergistic effects of co-delivered drugs. Additionally, the combination treatment groups showed a significant reduction in tumor size and lung metastasis compared to the monotherapy and control groups. These findings underscore the potential of the nanocomposite used to develop a novel co-delivery system to enhance therapeutic outcomes, reduce side effects, and provide a promising new strategy for future cancer treatments. Abstract Background Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance and significant side effects. Combination therapies, coupled with nanotechnology-based co-delivery systems, offer enhanced efficacy by targeting multiple pathways in cancer progression. In this study, we developed an injectable, stimuli-responsive nanosystem using a chitosan hydrogel embedded with mesoporous silica nanoparticles for the co-administration of 5-fluorouracil and everolimus. This approach aims to optimize controlled drug release, enhance the synergistic anticancer effect, and overcome challenges associated with co-loading different therapeutic agents. Methods Various techniques were employed to characterize the nanoparticles and the hydrogel. Cell uptake, apoptosis, and proliferation of 4T1 breast cancer cells were evaluated by flow cytometry and Resazurin assay, respectively. The Balb/C mice model of breast cancer, which received the therapeutical nanoplatforms subcutaneously near the tumoral region was used to examine tumor size and lung metastases. Results The results revealed that the nanoparticles had a suitable loading capacity and high cellular uptake. The drug release was pH-sensitive and synergistic. By incorporating nanoparticles into the hydrogel, the cell death rate and apoptosis of 4T1 breast cancer cells increased significantly, due to the synergistic effects of co-delivered drugs. Additionally, the combination treatment groups showed a significant reduction in tumor size and lung metastasis compared to the monotherapy and control groups. Conclusions These findings underscore the potential of the nanocomposite used to develop a novel co-delivery system to enhance therapeutic outcomes, reduce side effects, and provide a promising new strategy for future cancer treatments. |
| ArticleNumber | 382 |
| Audience | Academic |
| Author | Bijad, Elham Deris, Fatemeh Soltani, Amin Khosravian, Pegah Jafari, Raziyeh Amiri, Niloufar Taheri, Fatemeh Dehkordi, Ebrahim Soleiman Alizadeh, Akram Chermahini, Fatemeh Amini Arvejeh, Pooria Mohammadi Marincola, Francesco Mirzaei, Seyed Abbas |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/40165241$$D View this record in MEDLINE/PubMed |
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Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug... Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug resistance... Background Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such as drug... Abstract Background Breast cancer remains one of the leading causes of death among women globally, with traditional therapies often limited by challenges such... |
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| SubjectTerms | Animals Antineoplastic Combined Chemotherapy Protocols - therapeutic use Apoptosis - drug effects Biomedical and Life Sciences Biomedicine Breast cancer Breast neoplasm Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cell Line, Tumor Cell Proliferation - drug effects Chemical properties Chitin Chitosan - chemistry Dosage and administration Drug delivery Drug Delivery Systems Drug Liberation Drug therapy Drugs Everolimus - administration & dosage Everolimus - pharmacology Everolimus - therapeutic use Female Fluorouracil Fluorouracil - administration & dosage Fluorouracil - pharmacology Fluorouracil - therapeutic use Health aspects Humans Hydrogels Hydrogels - chemistry Innovations Medicine/Public Health Mesopores Mice Mice, Inbred BALB C Nanobiomaterials & Nanomedicine Nanocomposite Nanoparticles Nanoparticles - chemistry Nanoparticles - ultrastructure Porosity Silicon Dioxide - chemistry Synergism Vehicles |
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| Title | A novel approach for the co-delivery of 5-fluorouracil and everolimus for breast cancer combination therapy: stimuli-responsive chitosan hydrogel embedded with mesoporous silica nanoparticles |
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