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Journal Article
Research Support, Non-U.S. Gov't
Evaluation of the antitumor effects of vitamin K 2 (menaquinone-7) nanoemulsions modified with sialic acid-cholesterol conjugate.
Drug Delivery and Translational Research 2018 Februrary
Numerous studies have recently shown that vitamin K2 (VK2 ) has antitumor effects in a variety of tumor cells, but there are few reports demonstrating antitumor effects of VK2 in vivo. The antitumor effects of VK2 in nanoemulsions are currently not known. Therefore, we sought to characterize the antitumor potential of VK2 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 VK2 distribution to the tumor tissue. VK2 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 VK2 nanoemulsions significantly suppressed the tumor growth. The VK2 nanoemulsions modified with sialic acid-cholesterol conjugate showed higher tumor growth suppression than the VK2 nanoemulsions, while neither of them exhibited signs of drug toxicity. In summary, VK2 exerted effective antitumor effects in vivo, and VK2 nanoemulsions modified with sialic acid-cholesterol conjugate enhanced the antitumor activity, suggesting that these VK2 may be promising agents for the prevention or treatment of tumor in patients.
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