抄録
α-Tocopheryl succinate (TS) has attracted attention as a unique anti-cancer drug for its ability to induce apoptosis in various cancer cells. Furthermore, TS itself readily forms nanovesicles (TS-NVs) and is a prospective tool for use as an antitumor drug delivery system. Activation of various signal transduction factors is also a well-known function of TS. In particular, protein kinase C (PKC), which acts in upstream in the signal transduction, is thought to play an important role in the effects of TS. Our theoretical computational study indicates that TS activates PKC by direct interaction with PKC due to its high structural flexibility. However, TS-NVs are unstable for encapsulating drugs and passive targeting delivery to tumor tissues via an enhanced permeation and retention (EPR) effect. Therefore, to improve the stability of vesicles, we developed a novel nanovesicle consisting of TS and egg phosphatidylcholine (TS-EPC-NVs). The in vivo antitumor activity of TS-EPC-NVs was more potent than that of TS-NVs. Moreover, the in vitro anticancer efficiency of TS-EPC-NVs increased seven-fold. In addition, TS-EPC-NVs encapsulating siRNA showed significant knockdown efficiency. In conclusion, TS-EPC-NVs represent a novel and attractive drug delivery system carrier. It is expected that the drug delivery system shows synergistic anti-tumor activity of the encapsulated drug and the carrier itself.
