5-Fluorouracil-β-Cyclodextrin conjugates:Linker strategies to enhance the anticancer efficacy and reduce the side effects
5-Fluorouracil (5-FU) serves as a first-line therapeutic agent for colorectal cancer, however, its utility is limited by a short half-life and significant cytotoxicity. This study focused on the construction of 5-Fluorouracil-β-Cyclodextrin polymers (5-FUSA-β-CD and 5-FUBA-β-CD) by covalent conjugat...
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Elsevier
2025-03-01
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| Series: | Carbohydrate Polymer Technologies and Applications |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666893925000301 |
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| author | Liangliang Hu Ting Meng Davies Marabada Zhichao Jin Qing Huang Shijie Wei Zhizhong Wang |
| author_facet | Liangliang Hu Ting Meng Davies Marabada Zhichao Jin Qing Huang Shijie Wei Zhizhong Wang |
| author_sort | Liangliang Hu |
| collection | DOAJ |
| description | 5-Fluorouracil (5-FU) serves as a first-line therapeutic agent for colorectal cancer, however, its utility is limited by a short half-life and significant cytotoxicity. This study focused on the construction of 5-Fluorouracil-β-Cyclodextrin polymers (5-FUSA-β-CD and 5-FUBA-β-CD) by covalent conjugation using linker strategies to address limitations. The cytotoxicity assays on human colon cancer cell lines HT-29 and normal colon epithelial cells NCM-460 demonstrated that the IC50 value of the 5-FUBA-β-CD conjugate for the HT-29 cells was 38.72 ± 0.13 μM, indicating superior antitumor activity compared to both 5-FUBA-β-CD and 5-FU. Additionally, the conjugate exhibited reduced cytotoxicity towards normal colon epithelial cells. Pharmacokinetic analyses revealed that 5-FUSA-β-CD and 5-FUBA-β-CD were eliminated slowly and their half-lives were longer than that of free 5-FU. Distinct linkers were meticulously designed and synthesized to generate 5-Fluorouracil-β-Cyclodextrin conjugates that exhibit differential anti-colon cancer activity and half-lives. These findings not only demonstrated that 5-Fluorouracil-β-Cyclodextrin conjugates exhibits superior antitumor activity and reduced toxicity but also suggest that the linker plays a crucial role in determining both the efficacy of drug conjugates as an anticancer agent and its associated adverse effects. Future designs of linker can be optimized for greater efficiency. |
| format | Article |
| id | doaj-art-3ff224f8374646dfa772f655bc30e353 |
| institution | Kabale University |
| issn | 2666-8939 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Carbohydrate Polymer Technologies and Applications |
| spelling | doaj-art-3ff224f8374646dfa772f655bc30e3532025-02-11T04:35:32ZengElsevierCarbohydrate Polymer Technologies and Applications2666-89392025-03-0191006915-Fluorouracil-β-Cyclodextrin conjugates:Linker strategies to enhance the anticancer efficacy and reduce the side effectsLiangliang Hu0Ting Meng1Davies Marabada2Zhichao Jin3Qing Huang4Shijie Wei5Zhizhong Wang6School of Pharmacy, Ningxia Medical University, Ningxia, Yinchuan, ChinaSchool of Pharmacy, Ningxia Medical University, Ningxia, Yinchuan, ChinaSchool of Pharmacy, Ningxia Medical University, Ningxia, Yinchuan, ChinaSchool of Pharmacy, Ningxia Medical University, Ningxia, Yinchuan, China; Corresponding authors.School of Pharmacy, Ningxia Medical University, Ningxia, Yinchuan, China; Corresponding authors.Department of Pharmacy, General Hospital, Ningxia Medical University, Yinchuan, 750004, China; Corresponding authors.School of Pharmacy, Ningxia Medical University, Ningxia, Yinchuan, China; Corresponding authors.5-Fluorouracil (5-FU) serves as a first-line therapeutic agent for colorectal cancer, however, its utility is limited by a short half-life and significant cytotoxicity. This study focused on the construction of 5-Fluorouracil-β-Cyclodextrin polymers (5-FUSA-β-CD and 5-FUBA-β-CD) by covalent conjugation using linker strategies to address limitations. The cytotoxicity assays on human colon cancer cell lines HT-29 and normal colon epithelial cells NCM-460 demonstrated that the IC50 value of the 5-FUBA-β-CD conjugate for the HT-29 cells was 38.72 ± 0.13 μM, indicating superior antitumor activity compared to both 5-FUBA-β-CD and 5-FU. Additionally, the conjugate exhibited reduced cytotoxicity towards normal colon epithelial cells. Pharmacokinetic analyses revealed that 5-FUSA-β-CD and 5-FUBA-β-CD were eliminated slowly and their half-lives were longer than that of free 5-FU. Distinct linkers were meticulously designed and synthesized to generate 5-Fluorouracil-β-Cyclodextrin conjugates that exhibit differential anti-colon cancer activity and half-lives. These findings not only demonstrated that 5-Fluorouracil-β-Cyclodextrin conjugates exhibits superior antitumor activity and reduced toxicity but also suggest that the linker plays a crucial role in determining both the efficacy of drug conjugates as an anticancer agent and its associated adverse effects. Future designs of linker can be optimized for greater efficiency.http://www.sciencedirect.com/science/article/pii/S26668939250003015-fluorouracilConjugatesLinker;β-cyclodextrinAntitumor activityCytotoxicity |
| spellingShingle | Liangliang Hu Ting Meng Davies Marabada Zhichao Jin Qing Huang Shijie Wei Zhizhong Wang 5-Fluorouracil-β-Cyclodextrin conjugates:Linker strategies to enhance the anticancer efficacy and reduce the side effects Carbohydrate Polymer Technologies and Applications 5-fluorouracil Conjugates Linker;β-cyclodextrin Antitumor activity Cytotoxicity |
| title | 5-Fluorouracil-β-Cyclodextrin conjugates:Linker strategies to enhance the anticancer efficacy and reduce the side effects |
| title_full | 5-Fluorouracil-β-Cyclodextrin conjugates:Linker strategies to enhance the anticancer efficacy and reduce the side effects |
| title_fullStr | 5-Fluorouracil-β-Cyclodextrin conjugates:Linker strategies to enhance the anticancer efficacy and reduce the side effects |
| title_full_unstemmed | 5-Fluorouracil-β-Cyclodextrin conjugates:Linker strategies to enhance the anticancer efficacy and reduce the side effects |
| title_short | 5-Fluorouracil-β-Cyclodextrin conjugates:Linker strategies to enhance the anticancer efficacy and reduce the side effects |
| title_sort | 5 fluorouracil β cyclodextrin conjugates linker strategies to enhance the anticancer efficacy and reduce the side effects |
| topic | 5-fluorouracil Conjugates Linker;β-cyclodextrin Antitumor activity Cytotoxicity |
| url | http://www.sciencedirect.com/science/article/pii/S2666893925000301 |
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