Sorafenib loaded ZIF-8 metal-organic frameworks as a multifunctional nano-carrier offers effective hepatocellular carcinoma therapy

Abstract

Hepatocellular carcinoma (HCC) is a primary malignant neoplasia of the liver and sorafenib is one of the most commonly used drugs in the treatment of HCC. Due to undesirable nature and side effects of sorafenib, nano-drug delivery systems are being developed. A member of metal-organic frameworks (MOFs), ZIF-8 offers a very suitable platform for drug transport and controlled drug release due to its zinc content and pH-sensitive, biodegradable in an acidic environment. In the present study, sorafenib was encapsulated in ZIF-8 material with 53.8% efficiency and 58% loading capacity (SRF@ZIF-8). Structural characterizations of synthesized ZIF-8 and SRF@ZIF-8 system were investigated in details. Drug release analysis exhibited a faster release profile at pH 5.0 compared to that of pH 7.4. The cytotoxic effects of sorafenib and zinc were investigated in HepG2 and HuH-7 cell lines in vitro. The results demonstrated that in addition to sorafenib, ZIF-8 provided zinc to the envi-ronment with its biodegradable structure resulted in an effective cytotoxic effect on HCC cells. The findings showed that a formulation combining zinc and sorafenib together was more effective in HCC treatment compared to sorafenib itself.