In this light, the aim of the present study was to develop an improved targeted therapy for melanoma using an optimized nano-system based on Il-13-conjugated long-circulating liposomes containing SIM (Il-13-LCL-SIM) to target TAMs and PEG-stabilized EVs containing DOX (PEG-EV-DOX) to target melanoma cells. Here, IL13 is linked to melanoma.