Co-delivery of doxorubicin and epacadostat via heparin coated pH-sensitive liposomes to suppress the lung metastasis of melanoma

High metastasis is responsible for the failure in the treatment of melanoma . Chemoimmunotherapy has shown conspicuous inhibition effects not only on the growth of tumor in situ, but also on the metastasis to distant organs. Given that the indoleamine-2,3 dioxygenase (IDO) overexpressed in the microenvironment of tumor leads to the immune escape, the combination of chemotherapeutic drug and IDO inhibitor might be a promising chemoimmunotherapy. Besides, the hematogenous metastasis mediated by platelets was supposed to be blocked by the heparin (HP). Therefore, a drug delivery system with all these elements involved might be a potential treatment for melanoma. Here, we developed a pH-sensitive liposomal dual-delivery system for doxorubicin (DOX) and epacadostat (EPA) with HP coated (HP/LDE). It was confirmed to enhance cytotoxicity and apoptosis , reverse the platelets-activated epithelial mesenchymal transformation (EMT) and prevent the invasion and migration in vitro . After systemic administration , HP/LDE provided the optimum anti-metastasis effect on the melanoma. The results of evaluation on DC maturation, CD8 + cytotoxic T lymphocytes (CTLs) activation and T cell mediated cytotoxicity were consistent in vitro and in vivo . Taken together, our study established a functional liposomal dual-delivery system with ideal anti-metastasis efficacy on melanoma.