Hyaluronic acid-conjugated lipoplexes for targeted delivery of siRNA in a murine metastatic lung cancer model

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• 作者：Thais Leite Nascimento^a ; ^b ; ^c ; Hervé ; Hillaireau^a ; ^b ; Juliette Vergnaud^a ; ^b ; Melania Rivano^a ; ^b ; Claudine Delomé ; nie^d ; Delphine Courilleau^d ; Silvia Arpicco^e ; Jung Soo Suk^f ; ^g ; ^h ; Justin Hanes^f ; ^g ; ^h ; Elias Fattal^a ; ^b ; ^{elias.fattal@u-psud.fr" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Lipoplexes ; siRNA ; Hyaluronic acid ; A549 ; CD44 ; Luciferase
• 刊名：International Journal of Pharmaceutics
• 出版年：2016
• 出版时间：30 November 2016
• 年：2016
• 卷：514
• 期：1
• 页码：103-111
• 全文大小：1404 K

文摘

We have investigated the impact of hyaluronic acid (HA)-coating on the targeting capacity of siRNA lipoplexes to CD44-overexpressing tumor cells. Cellular uptake and localization of HA-lipoplexes were evaluated by flow cytometry and fluorescence microscopy and both methods showed that these lipoplexes were rapidly internalized and localized primarily within the cytoplasm. Inhibition of luciferase expression on the A549-luciferase lung cancer cell line was achieved in vitro using an anti-Luc siRNA. 81% of luciferase gene expression inhibition was obtained in vitro with HA-lipoplexes at +/− ratio 2. In vivo, in a murine A549 metastatic lung cancer model, the treatment with HA-lipoplexes carrying anti-luciferase siRNA led to a statistically significant decrease of luciferase expression as opposed to progressive increase with non-modified lipoplexes or NaCl 0.9%. The reduction of the expression of luciferase mRNA tumor of mice treated with HA-lipoplexes supported the inhibition effect due to siRNA. These results highlight the potential of HA-lipoplexes in CD44-targeting siRNA delivery.