siRNA的抗体靶向递送的超分子生物缀合策略
Supramolecular Bioconjugation Strategy for Antibody-Targeted Delivery of siRNA
影响因子:3.90000
分区:化学2区 / 生化研究方法2区 有机化学2区 生化与分子生物学3区 化学：综合3区
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
摘要
RNA干扰是一种广泛使用的生物学过程，通过该过程，双链RNA通过靶向mRNA降解来诱导序列特异性基因沉默。但是，siRNA的物理化学特性使它们的交付极具挑战性，从而限制了他们在目标部位的生物利用度。在这种情况下，我们开发了曲妥珠单抗偶联的纳米载体的多功能和选择性siRNA输送系统。这些免疫偶联物由寡核苷酸改性抗体与阳离子胶束的静电相互作用组成，用于在HER2过表达的癌细胞中靶向siRNA的靶向递送。结果表明，当与适当的N/P比相应的siRNA相关联时，我们的超分子组件能够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。
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.