An ionic liquid nanoemulsion transdermal delivery system for targeted melanoma therapy

Melanoma is the deadliest form of skin malignancy. The existing transdermal treatment strategies are difficult to achieve effective concentration of drugs in deep-seated tumors, which seriously affects the effect of percutaneous treatment. The low efficacy of medications for treating melanoma and their percutaneous penetration into tumor tissues are the urgent problems to be solved in percutaneous treatment of skin malignancies. In this work, two dacarbazine/benzothiocycloheptane (DTIC/14) couplets were designed and synthesized, among which compound HIT-1 exhibited significantly cytotoxicity to B16-F10 (IC₅₀ = 7.86 μM), and 10.3-fold stronger than DTIC. HIT-1 could significantly induce apoptosis and G0/G1 phase arrest of B16-F10 cells, showing a good anti-melanoma effect. Three self-assembled nanoemulsions (HIT-1/PM-MEs) were prepared on the basis of molecular simulation, among which HIT-1/PM-ME-1-1 had the best transdermal drug delivery effect. HIT-1/PM-ME-1-1 was not only 11.8-fold stronger than DTIC in terms of anti-B16-F10 activity, but also a good regulator of mRNA and protein expression of DNAJB1, HSPA1B, p53, Bcl-2 and Cleaved-caspase 3. Furthermore, the HIT-1/PM-ME-1-1 transdermal delivery system showed optimal antitumor effects and stimulated antitumor immune response. Altogether, these results strongly support that this transdermal drug delivery system provides a valuable new strategy for the treatment of cutaneous melanoma.