Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Pharmacy Department, Yamaguchi University Hospital, Yamaguchi, Japan.
J Drug Target. 2024 Aug;32(7):848-854. doi: 10.1080/1061186X.2024.2362361. Epub 2024 Jun 5.
In this study, we determined effects of an anionic siRNA delivery vector, siRNA ternary complex, which is constructed with biodegradable dendrigraft poly-L-lysine (DGL) and γ-polyglutamic acid (γ-PGA) on the melanoma cells and melanoma lung metastasis. The siRNA ternary complex showed high cellular uptake and silencing effect in melanoma cell line B16-F10/Luc cells. After intravenous administration of the siRNA ternary complex, high silencing effect was also observed in the lung of B16-F10/Luc melanoma metastasis model mice. Therefore, we applied vascular endothelial growth factor (VEGF)-siRNA on the siRNA ternary complex and determined the effect on the melanoma lung metastasis. The siRNA ternary complex containing VEGF-siRNA reduced VEGF protein levels significantly in and , and the complex successfully inhibited melanoma lung metastasis. This biodegradable and effective siRNA delivery vector, siRNA ternary complex, could be available for clinical trials.
在这项研究中，我们确定了阴离子 siRNA 递药载体——由可生物降解的树枝状接枝聚赖氨酸（DGL）和γ-聚谷氨酸（γ-PGA）构建的 siRNA 三元复合物，对黑素瘤细胞和黑素瘤肺转移的影响。该 siRNA 三元复合物在黑素瘤细胞系 B16-F10/Luc 细胞中表现出高细胞摄取和沉默效果。静脉注射 siRNA 三元复合物后，在 B16-F10/Luc 黑素瘤转移模型小鼠的肺部也观察到了高沉默效果。因此，我们在 siRNA 三元复合物上应用血管内皮生长因子（VEGF）-siRNA，并确定其对黑素瘤肺转移的影响。含 VEGF-siRNA 的 siRNA 三元复合物可显著降低 和 中的 VEGF 蛋白水平，该复合物成功抑制了黑素瘤肺转移。这种可生物降解且有效的 siRNA 递药载体——siRNA 三元复合物，可用于临床试验。
