Evaluation of the antitumor effects of vitamin K (menaquinone-7) nanoemulsions modified with sialic acid-cholesterol conjugate.

Numerous studies have recently shown that vitamin K (VK) has antitumor effects in a variety of tumor cells, but there are few reports demonstrating antitumor effects of VK in vivo. The antitumor effects of VK in nanoemulsions are currently not known. Therefore, we sought to characterize the antitumor potential of VK nanoemulsions in S180 tumor cells in the present study. Furthermore, a ligand conjugate sialic acid-cholesterol, with enhanced affinity towards the membrane receptors overexpressed in tumors, was anchored on the surface of the nanoemulsions to increase VK distribution to the tumor tissue. VK was encapsulated in oil-in-water nanoemulsions, and the physical and chemical stability of the nanoemulsions were characterized during storage at 25 °C. At 25 °C, all nanoemulsions remained physically and chemically stable with little change in particle size. An in vivo study using syngeneic mice with subcutaneously established S180 tumors demonstrated that intravenous or intragastric administration of VK nanoemulsions significantly suppressed the tumor growth. The VK nanoemulsions modified with sialic acid-cholesterol conjugate showed higher tumor growth suppression than the VK nanoemulsions, while neither of them exhibited signs of drug toxicity. In summary, VK exerted effective antitumor effects in vivo, and VK nanoemulsions modified with sialic acid-cholesterol conjugate enhanced the antitumor activity, suggesting that these VK may be promising agents for the prevention or treatment of tumor in patients.