Abstract
Sorafenib is a multikinase inhibitor approved for several cancers, including hepatocellular carcinoma (HCC). Sorafenib is also used as anti-agiogenesis therapy in many study. However, sorafenib still faces several problems such as poor pharmacokinetics and resistance mechamism. Due to limited efficacy of Sorafenib, we introduced an adjuvant to overcome the ressistant mechanisms and thus synergistically elevate the therapeutic effect. Nitric oxide (NO) is a well-known endogenous signaling molecule. NO could regulate many biological functionl, including agiogenesis, proliferation, apopoptosis and immune responses. According to the previous study, NO is also a highly reactive molecule which has potential to serve as an anti-cancer drug. In this study, we used dinitrosyl iron complexes (SEt) as a NO donor to deliver NO into the cancer cells. We successfully inhibited the liver cancer cell growth by treatment of combined SEt and sorafenib in vitro. The protein expression of pAkt was also down-regulated by the combication treatment. Futhermore, we developed a tumor-targeted PLGA nanoparticles to co-deliver SEt and sorafneib into hepatocellular carcinoma (HCC). We showed the nanoscale combination therapy could efficiently inhibit the tumor growth in vivo.