Exosomes improved the in vitro anti-melanoma efficacy of dihydroartemisinin

Abstract

Melanoma is the most aggressive and highly metastatic type of skin cancer, with few available therapeutic options. Chemotherapy and radiation therapy are the cornerstone options for the treatment of melanoma. However, chemotherapy causes several adverse effects, as most are administered via the parenteral route. Hence it is indispensable to discover new compounds for the treatment of melanoma. Dihydroartemisinin (DHA) is a semi-synthetic and active metabolite of all artemisinin compounds that is FDA-approved for the treatment of malaria. Apart from the anti-malarial activity, DHA has several other pharmacological activities, including anticancer activity. Despite the good anticancer property, DHA has solubility and toxicity issues that hinder the activity of DHA. To address these issues, we developed an exosomal formulation of DHA to further improve the anticancer efficacy in vitro. Exosomes were isolated from bovine milk, and DHA was loaded by the sonication method. The size was found to be approximately 100 nm and exhibited a spherical shape under scanning and atomic force microscopy. The exosomes further exhibited burst release, followed by sustained release in pH 7.4 and 5.5. The Exo-DHA showed increased anticancer activity as confirmed by various in vitro assays, such as cytotoxicity, cellular uptake, DNA fragmentation, reactive oxygen species, mitochondrial membrane potential, and colony formation assays. Furthermore, the transwell migration and scratch assay further confirmed the anti-migration property of Exo-DHA. Hence, from the obtained data, it was concluded that the anticancer efficacy of DHA was improved when loaded into bovine milk-derived exosomes. Despite the good in vitro results, further in vivo investigations are required. © 2024