Preparation of RGD-modified liposomes encapsulated with shikonin and its targeted anti-melanoma effects

Melanoma is the most aggressive skin tumor, and conventional treatment is ineffective. Studies have shown that shikonin, derived from the traditional Chinese medicine Lithospermum erythrorhizon , has various anticancer activities. In this work, RGD- modified liposomes encapsulated with shikonin (RGD-Lip-SHK) were prepared by thin- film dispersion, which could highly recognize the integrin α V β 3 on the surface of melanoma cells. RGD-Lip-SHK appeared as spheroid-like vesicles with a particle size of approximately 120 nm, and its ξ-potential was negative. RGD-Lip-SHK remained stable in serum within 48 h and possessed sustained-release effect. In vitro , compared with non -targeted liposomes (Lip-SHK), RGD-Lip-SHK was more efficiently taken up, had higher cytotoxicity, was better targeted to inhibit cell growth, migration, and invasion, and boost cell apoptosis by regulating the expression of Bcl-2 and Bax proteins in melanoma cells. In vivo , RGD-Lip-SHK had the strongest targeted anti-melanoma effect by α V β 3 -mediated endocytosis with a long circulation time and inhibited tumor growth in B16F10 tumor-bearing mice compared to other groups. Furthermore, the histology of major organs and the body weight of mice showed that RGD-Lip-SHK had less toxicity. In summary, these results indicated that RGD-Lip-SHK has great potential for the targeted treatment of melanoma, and is expected to become a novel and highly effective strategy for tumor-targeted therapy.