Abstract: OBJECTIVE To prepare a novel itraconazole liposome modified by ginsenoside Rk1(R-ITZ-Lip) for tumor therapy and investigate its antitumor efficacy in vitro and in vivo. METHODS R-ITZ-Lip was prepared by reverse evaporation method, and its particle size, Zeta potential, encapsulation efficiency were investigated. The in vitro and in vivo tumor targeting of R-ITZ-Lip was evaluated by fluorescence microscopy, flow cytometry and in vivo and in vitro imaging experiments. MTT cytotoxicity tests and tumor growth inhibitory rate were used to evaluate the antitumor efficacy in vitro and in vivo. RESULTS R-ITZ-Lip showed a rounded morphology with average particle size of (124.67±2.05)nm and encapsulation efficiency of (97.49±1.93)%. The cellular uptake experiments showed that R-ITZ-Lip could be better taken up by mouse triple-negative breast cancer 4T1 cells, and the in vivo and in vitro fluorescence imaging results showed that the distribution of R-ITZ-Lip in tumor sites was significantly enhanced in 4T1 xenograft mouse model. In the MTT cytotoxicity tests, R-ITZ-Lip showed concentration-dependent cytotoxicity to 4T1 cells with IC₅₀ of 1.37 μg·mL^-1, which was much lower than that of 3.12 μg·mL^-1 of the itraconazole cholesterol liposomes(C-ITZ-Lip). In the 4T1 xenograft model, R-ITZ-Lip more effectively inhibited the tumor growth, angiogenesis and malignant proliferation of tumor cells. The tumor inhibition rate of R-ITZ-lip group was 83.54%, which was significantly better than that of C-ITZ-lip group(73.87%) and ITZ injection group(57.86%). CONCLUSION R-ITZ-Lip is constructed for tumor therapy, which exhibits the characteristics of improved pharmacologic properties, precise tumor targeting and enhanced therapeutic effect.