Liposomal formulations of novel metal-based complexes exhibiting high antitumor activity against melanoma

Melanoma is the most aggressive skin cancer and, despite therapeutic advances in recent years, it continues to be associated with the highest mortality rates. Thus, the development of more effective and safer treatment options remain imperative. In this context, and driven by the discovery of the antineoplastic properties and consequent clinical approval of cisplatin, metal-based complexes have gained increasing attention. In this work, previously synthesized vanadium and nickel-based complexes which exhibited cytotoxic activity towards melanoma cell lines in their free form, were incorporated into liposomes to improve solubility and enhance tumor cell selectivity. Nickel-based nanoformulations showed higher loading capacity than the vanadium complex and were therefore selected for further studies. The optimized nickel lipid nanoformulation was tested in vitro regarding antiproliferative properties and cellular mechanism of action in B16F10 and A375 melanoma cells. Lastly, the therapeutic potential and the biodistribution profile were also evaluated in an in vivo syngeneic murine melanoma model. In vitro studies demonstrated that 24 and 48 h after incubation in melanoma cell lines, the nickel-based complex retained its antiproliferative activity following association with liposomes. Furthermore, the liposomal formulation promoted cell cycle arrest in G2/M phase in both cell lines, while hemolytic assays demonstrated its safety for intravenous administration. Finally, in vivo proof of concept studies confirmed that both the free and liposomal forms of the nickel-based complex significantly impaired tumor progression achieving effects comparable to the positive control 5-Fluorouracil, despite the latter being administered at a four-fold higher dose. Moreover, biodistribution studies revealed that labelled liposomes accumulated and persisted at tumor sites, thus correlating with the observed therapeutic effects. Overall, the safety and efficacy of this strategy highlight its strong potential for melanoma management.