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...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | Carbohydrate Polymer Technologies and Applications |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666893925000301 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| Summary: | 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. |
|---|---|
| ISSN: | 2666-8939 |