Fan Lixin, Yu Yang, Shi Kunpeng, Hu Yanqiu, Hou Xingyu, Sun Weitong
College of Pharmacy, Jiamusi University, Jiamusi, Heilongjiang, China.
Pharmacy Department, Jiamusi Infectious Disease Hospital, Jiamusi, Heilongjiang, China.
Ther Deliv. 2025 Jul;16(7):637-649. doi: 10.1080/20415990.2025.2513223. Epub 2025 May 30.
The presence of overexpressed folate-receptor and high concentration of glutathione (GSH) in liver cancer cells has been exploited and we have synthesized Folic acid-Dextran-Cystamine-Stearic acid (FDCS) for efficient and multifunctional delivery of the drug sorafenib (SAF) to enhance the anticancer effects.
The characteristics of micelles such as physicochemical properties and in vitro release were investigated. The pharmacokinetic characteristics of the micelle and SAF groups in rats were investigated. In vitro and in vivo anti-tumor experiments were performed with HepG2 cells.
SAF-FDCS was successfully prepared and characterized. The cellular experiments showed that SAF-FDCS significantly enhanced the toxicity and inhibitory effects on HepG2 cells compared with free drug and the other micelles without smart response, and the uptake capacity of cellular HepG2 for SAF-FDCS was significantly higher than the groups without folic acid. Pharmacokinetic results showed that SAF-FDCS revealed a longer circulation time than free SAF. In addition, the tumor inhibition rate of SAF-FDCS in the subcutaneous graft tumor model of HepG2 cells was 84.6%, significantly higher than in other groups.
These results demonstrated the feasibility of SAF-FDCS micelles in inhibiting tumor growth and their superiority in anti-cancer effects compared to free drugs and normal micelles.
利用肝癌细胞中过表达的叶酸受体和高浓度的谷胱甘肽（GSH），我们合成了叶酸-葡聚糖-胱胺-硬脂酸（FDCS），用于高效多功能地递送药物索拉非尼（SAF），以增强抗癌效果。
研究了胶束的物理化学性质和体外释放等特性。考察了大鼠体内胶束组和SAF组的药代动力学特征。用HepG2细胞进行了体外和体内抗肿瘤实验。
成功制备并表征了SAF-FDCS。细胞实验表明，与游离药物和其他无智能响应的胶束相比，SAF-FDCS显著增强了对HepG2细胞的毒性和抑制作用，且HepG2细胞对SAF-FDCS的摄取能力明显高于无叶酸的组。药代动力学结果表明，SAF-FDCS的循环时间比游离SAF长。此外，SAF-FDCS在HepG2细胞皮下移植瘤模型中的肿瘤抑制率为84.6%，显著高于其他组。
这些结果证明了SAF-FDCS胶束在抑制肿瘤生长方面的可行性，以及与游离药物和普通胶束相比在抗癌效果上的优越性。
