Microalgal Exosome-like Nanovesicles from Nannochloropsis oculata Attenuate Melanogenesis Through Tyrosinase Inhibition in B16-F10 Melanoma Cells

As primary producers in aquatic ecosystems, microalgae function not only as a natural source of nourishment for several economically important aquatic species but also as reservoirs of bioactive molecules. Microalgae can secrete exosome-like nanoparticles that transport functional biomolecules, such as proteins and nucleic acids, into the extracellular milieu, thereby mediating intercellular signaling and eliciting ecological or biomedical responses. Although plant-derived exosome-like nanoparticles have attracted attention for their utility in drug delivery and dermatology, the functional properties of microalgae-derived nanoparticles-particularly from species extensively applied in aquaculture-remain inadequately characterized. In this study, exosome-like nanovesicles were isolated from <i>Nannochloropsis oculata</i> (N-ELNs), a microalgal species widely used in aquaculture, and their skin-whitening potential was evaluated using the B16-F10 mouse melanoma cell model. The highest N-ELN yield was observed during the adaptation, exponential, and stationary growth phases. Uptake analyses confirmed the efficient internalization of N-ELNs by B16-F10 cells. Cell counting kit-8 assays indicated that N-ELNs exhibited no cytotoxic effects on melanoma cells or normal human dermal fibroblasts (HFF-1). Scratch wound healing assays revealed that N-ELNs exerted no significant effect on cellular migration. In B16-F10 cells, N-ELNs suppressed tyrosinase activity by downregulating <i>Mitf</i> and its downstream genes <i>Tyr</i> and <i>Tyrp1</i>, resulting in a substantial reduction in melanin synthesis (<i>p</i> < 0.05). The inhibitory effects of N-ELNs on melanin production, tyrosinase activity, and gene expression of <i>Tyr</i>, <i>Tyrp1</i>, and <i>Mitf</i> were comparable to those of the positive control, arbutin. Collectively, these findings suggest that <i>N. oculata</i> exhibits promising skin-whitening properties, providing a novel perspective for clinical applications and supporting the high-value utilization of the microalgae aquaculture industry.