Supramolecular Bioconjugation Strategy for Antibody-Targeted Delivery of siRNA.

IF 4 2区 化学 Q1 BIOCHEMICAL RESEARCH METHODS
Manon Ripoll, Héloïse Cahuzac, Igor Dovgan, Sylvain Ursuegui, Patrick Neuberg, Stephane Erb, Sarah Cianférani, Antoine Kichler, Jean-Serge Remy, Alain Wagner
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引用次数: 0

Abstract

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.

用于抗体靶向递送 siRNA 的超分子生物共轭策略。
RNA 干扰是一种广泛应用的生物学过程,双链 RNA 通过靶向降解 mRNA 来诱导序列特异性基因沉默。然而,siRNA 的物理化学特性使其输送极具挑战性,从而限制了其在靶点的生物利用率。在这种情况下,我们开发了一种由曲妥珠单抗共轭的纳米载体组成的多功能、选择性 siRNA 递送系统。这些免疫共轭物由寡核苷酸修饰的抗体与阳离子胶束通过静电相互作用组装而成,用于在 HER2 表达缺失的癌细胞中靶向递送 siRNA。结果表明,当以适当的 N/P 比与相应的 siRNA 结合时,我们的超分子组合物能在体外以细胞选择性的方式有效地诱导荧光素酶和 PLK-1 基因沉默。
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来源期刊
CiteScore
9.00
自引率
2.10%
发文量
236
审稿时长
1.4 months
期刊介绍: Bioconjugate Chemistry invites original contributions on all research at the interface between man-made and biological materials. The mission of the journal is to communicate to advances in fields including therapeutic delivery, imaging, bionanotechnology, and synthetic biology. Bioconjugate Chemistry is intended to provide a forum for presentation of research relevant to all aspects of bioconjugates, including the preparation, properties and applications of biomolecular conjugates.
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