漆黄素 (Fis) 是一种具有抗癌作用的天然黄酮类化合物，但其输送受到限制。采用实验设计 (DoE) 方法，开发了非瑟酮纳米结构脂质载体 (NLC)，以更好地对抗转移性黑色素瘤。优化后的 NLC 粒径为 135.0 ± 5.5 nm，多分散指数 (PDI) 为 0.176 ± 0.035，包封率为 78.16 ± 1.58%。该制剂在 60 天内保持稳定，并在 96 小时内持续释放药物 (74.79 ± 3.75%)。与 Fis 相比，Fis-NLC 在 A-375 和 B16F10 细胞中 48 小时时的 IC50 值至少低约 3.2 倍，药物摄取高出约 1.8 倍。它还抑制黑色素瘤细胞的迁移性并诱导细胞周期停滞在 G1/S 期。逆转录酶聚合酶链反应 (RT-PCR) 和蛋白质印迹结果显示 Nrf2/NQO1 基因表达增强，并且通过上调 BAX mRNA 表达产生凋亡效应。 BAX 和 p53 的蛋白质水平比纯 Fis 高约 2 倍。体内研究表明，对黑色素瘤相关的肺和肝转移的抑制作用分别高出 5.9 倍和 10.7 倍。这项研究的结果证明 Fis-NLC 是对抗黑色素瘤的有效工具。

Fisetin (Fis), a natural flavonoid with anticancer effects, suffers from delivery constraints. Fisetin-nanostructured lipid carriers (NLCs) were developed for better efficacy against metastatic melanoma, employing the design of experiment (DoE) approach. The optimized NLCs depict a particle diameter of 135.0 ± 5.5 nm, a polydispersity index (PDI) of 0.176 ± 0.035, and an entrapment efficiency of 78.16 ± 1.58%. The formulation was stable over a period of 60 days and demonstrated sustained release of the drug (74.79 ± 3.75%) over 96 h. Fis-NLCs depicted at least ∼3.2 times lower IC50 value and ∼1.8 times higher drug uptake at 48 h in A-375 and B16F10 cells compared to that of Fis. It also inhibited the mobility of melanoma cells and induced cell cycle arrest at the G1/S phase. Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blot results show enhanced expression of Nrf2/NQO1 genes and an apoptotic effect by the upregulation of BAX mRNA expression. The protein levels of BAX and p53 were ∼2-fold higher compared with that of pure Fis. In-vivo studies demonstrated 5.9- and 10.7-fold higher inhibition in melanoma-associated metastasis in the lungs and liver, respectively. The outcomes from this study demonstrated Fis-NLCs as an effective tool against melanoma.