College of Food Science, Heilongjiang Bayi Agricultural University, Daqing 163319, China; Daqing Center of Inspection and Testing for Rural Affairs Agricultural Products and Processed Products, Ministry of Agriculture and Rural Affairs, Heilongjiang Bayi Agricultural University, Daqing 163319, China; National Coarse Cereals Engineering Research Center, Daqing 163319, China.
Natural Product Research Center, Korea Institute of Science and Technology (KIST), Gangneung 25451, Republic of Korea; Department of Marine Food Science and Technology, Gangneung-Wonju National University, 120 Gangneung, Gangwon 210-702, Republic of Korea.
Int J Biol Macromol. 2024 Jul;273(Pt 1):133121. doi: 10.1016/j.ijbiomac.2024.133121. Epub 2024 Jun 12.
GFP, a sulfated polysaccharide extracted from Grateloupia filicina, exhibits remarkable immunomodulatory activity. To reduce the side effects of 5-fluorouracil (5-FU), GFP was employed as a macromolecular carrier to synthesize of GFP-C-5-FU by reacting with carboxymethyl-5-fluorouracil (C-5-FU). Subsequently, this new compound was reacted with folic acid (FA) through an ester bond, forming novel conjugates named GFP-C-5-FU-FA. Nuclear magnetic resonance analysis confirmed the formation of GFP-C-5-FU-FA. In vitro drug release studies revealed that the cumulative release rate of C-5-FU reached 46.9 % in phosphate buffer (pH 7.4) after 96 h, a rate significantly higher than that of the control groups, indicating the controlled drug release behavior of GFP-C-5-FU-FA. Additionally, in vitro anticancer assays demonstrated the potent anticancer activity of GFP-C-5-FU-FA conjugates, as evidenced by the reduced viability of HeLa and AGS cancer cells, along with increased levels of apoptosis and cellular uptake. Western blot analysis indicated that the GFP-C-5-FU-FA conjugate effectively enhanced phosphorylation in cancer cells through the NF-kB and MAPK pathways, thereby promoting apoptosis. These findings highlight the potential of folate-targeted conjugates in efficiently treating HeLa and AGS cancer cells in vitro and lay a robust theoretical groundwork for future in vivo anti-cancer research involving these cells.
GFP 是从石莼中提取的一种硫酸化多糖，具有显著的免疫调节活性。为了降低 5-氟尿嘧啶（5-FU）的副作用，将 GFP 用作大分子载体，通过与羧甲基-5-氟尿嘧啶（C-5-FU）反应合成 GFP-C-5-FU。随后，通过酯键将该新化合物与叶酸（FA）反应，形成名为 GFP-C-5-FU-FA 的新型缀合物。核磁共振分析证实了 GFP-C-5-FU-FA 的形成。体外药物释放研究表明，C-5-FU 的累积释放率在 96 小时后达到 46.9%的磷酸盐缓冲液（pH 7.4）中，这一速率明显高于对照组，表明 GFP-C-5-FU-FA 具有控制药物释放的行为。此外，体外抗癌实验表明 GFP-C-5-FU-FA 缀合物具有很强的抗癌活性，这表现为 HeLa 和 AGS 癌细胞活力降低，细胞凋亡和摄取增加。Western blot 分析表明，GFP-C-5-FU-FA 缀合物通过 NF-kB 和 MAPK 途径有效增强了癌细胞中的磷酸化，从而促进了细胞凋亡。这些发现突出了叶酸靶向缀合物在体外有效治疗 HeLa 和 AGS 癌细胞的潜力，并为未来涉及这些细胞的体内抗癌研究奠定了坚实的理论基础。
