研究动态
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用于抗体靶向递送 siRNA 的超分子生物共轭策略。

Supramolecular Bioconjugation Strategy for Antibody-Targeted Delivery of siRNA.

发表日期:2024 Sep 25
作者: Manon Ripoll, Héloïse Cahuzac, Igor Dovgan, Sylvain Ursuegui, Patrick Neuberg, Stephane Erb, Sarah Cianférani, Antoine Kichler, Jean-Serge Remy, Alain Wagner
来源: BIOCONJUGATE CHEMISTRY

摘要:

RNA 干扰是一种广泛使用的生物过程,双链 RNA 通过靶向 mRNA 降解来诱导序列特异性基因沉默。然而,siRNA 的物理化学特性使其递送极具挑战性,从而限制了它们在靶位点的生物利用度。在此背景下,我们开发了一种曲妥珠单抗偶联纳米载体的多功能、选择性 siRNA 递送系统。这些免疫缀合物由寡核苷酸修饰抗体与阳离子胶束通过静电相互作用组装而成,用于在 HER2 过表达癌细胞中靶向递送 siRNA。结果表明,当以适当的 N/P 比与相应的 siRNA 结合时,我们的超分子组装能够在体外以细胞选择性方式有效诱导荧光素酶和 PLK-1 基因沉默。
RNA interference is a widely used biological process by which double-stranded RNA induces sequence-specific gene silencing by targeting mRNA for degradation. However, the physicochemical properties of siRNAs make their delivery extremely challenging, thus limiting their bioavailability at the target site. In this context, we developed a versatile and selective siRNA delivery system of a trastuzumab-conjugated nanocarrier. These immunoconjugates consist of the assembly by electrostatic interactions of an oligonucleotide-modified antibody with a cationic micelle for the targeted delivery of siRNA in HER2-overexpressing cancer cells. Results show that, when associated with the corresponding siRNA at the appropriate N/P ratio, our supramolecular assembly was able to efficiently induce luciferase and PLK-1 gene silencing in a cell-selective manner in vitro.