Abstract 2877: Advanced properties of Vitamin D3 nanocarrier in cancer chemotherapy

Abstract

Abstract [Purpose] Vitamin D3 (VD3) is used to treat osteoporosis and causes rickets, osteomalacia and hypocalcemia as deficiencies. On the other hand, it has been reported that large intake of VD3 reduce carcinogenesis risk in colorectal cancer, and VD3 itself has an anticancer effect. However, overdose of VD3 causes severe hypercalcemia as an adverse reaction. Therefore, it was expected that liposomalization of VD3 could improve this problem. VD3 encapsulated liposome as a drug nanocarrier is possible to accumulate of VD3 in a tumor as a target site without adverse reaction. In this study, the optimal preparation of VD3 encapsulated liposomes, their antitumor effects without adverse reaction were examined. [Methods] Cholecalciferol as VD3 encapsulated liposome by thin film method with different amount of cholesterol (CHO) was prepared. L-α-Distearoylphosphatidylcholine, CHO, L-α-distearoylphosphatidyl-DL-glycerol and 1-monomethoxypolyethyleneglycol-2,3-distearoylglyerol were dissolved using chloroform/methanol (4:1,(v/v)). After empty liposome preparation, VD3 is added to this suspension and incubated to encapsulate VD3 (Basic Method). The other method used ethanol as solvent and VD3 was added with the constituent lipids (Modified method). Cytotoxic effect was examined using tumor cell with overexpression of VD3 receptor. In P388 leukemia cell suspension, cytotoxicity by VD3 liposomes or VD3 solution were determined by the WST-8 assay. P388 leukemia cells with VD3 liposomes or VD3 solution were incubated and the intracellular VD3 concentration was measured. In vivo experiment, P388 leukemia cells bearing BDF1 mice were administered VD3 liposomes at 1st, 4th and 7th day. On the next day after final administration, tumor weight and blood calcium concentration were measured. [Results and Discussion] The particle size and zeta potential of VD3 liposomes were same level in some ratio of CHO in lipid composition. The encapsulated amount of VD3 in liposomes increased with the decrease of CHO amount. This may be due to the similar structure of CHO and VD3. VD3 encapsulated level of liposome by modified method was showed high amount. Because VD3 is lipophilicity, the high encapsulated amount of VD3 may have when the addition of VD3 with the formation of lipid film. VD3 receptor expression of P388 leukemia cells was higher than that of B16F10 melanoma cells by Western blots. In P388 leukemia cells, VD3 solution was not have cytotoxicity whereas VD3 liposome showed significant cytotoxicity. Furthermore, VD3 concentration in P388 leukemia cells was slight in VD3 solution group. In contrast, its concentration in VD3 liposome group quickly elevate and maintain a high concentration. In tumor bearing mice after VD3 liposome treatment, the tumor weight was decreased and the blood calcium concentration had lower level than that of control level. Namely, it was suggested that VD3 liposomes has a superior antitumor effect without the increase of adverse reaction. In conclusion, the optimum method of VD3 liposome preparation and its usefulness in novel cancer treatment were clarified. Citation Format: Yukako Soma, Ikumi Sugiyama, Yasuyuki Sadzuka. Advanced properties of Vitamin D3 nanocarrier in cancer chemotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2877.