5-Fluorouracil/curcumin loaded silk fibroin hydrogel for the adjuvant therapy in colorectal cancer

• Published in: Biomaterials advances 2025-03, Vol.168, p.214108, Article 214108
• Main Authors: Yuan, Jingxuan, Sun, Weiwei, Zhang, Zhibin, Wang, Yan, Huang, Dandan, Ren, Donglin, Chen, Hong, Wang, Xiaoqin, Li, Gang, Han, Zhifen
• Format: Article
• Language: English
• Subjects: Animals; Antineoplastic Agents - administration & dosage; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Chemotherapy, Adjuvant - methods; Colorectal cancer; Colorectal Neoplasms - drug therapy; Colorectal Neoplasms - pathology; Curcumin - administration & dosage; Curcumin - chemistry; Curcumin - pharmacology; Drug Carriers - chemistry; Drug Liberation; Drug loading; Fibroins - chemistry; Fibroins - pharmacology; Fluorouracil - administration & dosage; Fluorouracil - chemistry; Fluorouracil - pharmacology; HT29 Cells; Humans; Hydrogel; Hydrogels - chemistry; Nanosphere; Nanospheres - chemistry; Silk fibroin
• ISSN: 2772-9508; 2772-9508
• DOI: 10.1016/j.bioadv.2024.214108

This study employed silk fibroin (SF) as a carrier material to encapsulate curcumin (CUR) and 5-fluorouracil (5-FU), forming a highly effective drug-loaded hydrogel. The process involved mixing SF solution containing 5-FU with curcumin solution dissolved in acetone (AC), leading to the formation of composite drug-loaded nanospheres with particle sizes ranging from 77.87 nm to 299.22 nm, demonstrated enhanced permeability and retention (EPR) effects, enabling passive targeting of solid tumors. After the formation of the nanospheres, they were dispersed into a solution containing SF and polyethylene glycol (PEG). Following gelation and PEG removal, a SF hydrogel loaded with 5-FU and CUR (5-FU/CUR@SF hydrogel) was obtained. Results indicated that the 5-FU/CUR@SF hydrogel exhibited excellent drug release properties, with 5-FU and CUR achieving sustained release of 59.66 ± 3.76 % and 47.94 ± 5.03 %, respectively, over a 400-h of sustainable releasing period. Human colorectal cancer cell line (HT-29) and normal human colon epithelial cell line (NCM-460) were cultured with the 5-FU/CUR@SF hydrogel, resulting an apoptosis rate of only 17.38 ± 1.98 % for NCM-460 cells, whereas the apoptosis rate for HT-29 cells significantly increased to 72.31 ± 2.18 %, and its cell viability dropped to 59.77 ± 0.55 %. These findings suggest that the 5-FU/CUR@SF hydrogel exhibits low cytotoxicity toward normal NCM-460 cells, while exerting significant and sustained inhibitory effects on HT-29 cancer cells. In conclusion, the SF-based drug-loaded composite hydrogel holds great potential as a novel adjuvant therapeutic strategy for the treatment of CRC. •A novel SF/dual-drugs hydrogel shows sustained drug release properties.•Uniform SF nanospheres obtained by adjusting self-assembly conditions•Potently suppress the tumor cells but lower toxicity to normal cells•The drug hydrogel has potential as adjuvant therapeutic strategy for CRC.