Development of folic acid modified reduction-responsive micelles for the targeted release of sorafenib in liver cancer.

OBJECTIVE

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.

METHODS

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.

RESULTS

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.

CONCLUSIONS

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.