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Article Abstract

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.

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http://dx.doi.org/10.1080/1061186X.2024.2362361DOI Listing

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Article Synopsis
  • The study explored a new biodegradable siRNA delivery system made from dendrigraft poly-L-lysine and γ-polyglutamic acid, which was effective in targeting melanoma cells and metastasis.
  • The siRNA ternary complex demonstrated high cellular uptake and significantly silenced genes in melanoma cell lines and in mouse models after intravenous use.
  • Incorporating VEGF-siRNA into this delivery system led to reduced VEGF protein levels and effectively inhibited lung metastasis in melanoma, showing promise for future clinical trials.
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