Tommasini-Ghelfi Serena, Lee Andrew, Mirkin Chad A, Stegh Alexander H
Ken and Ruth Davee Department of Neurology, The Robert H. Lurie Comprehensive Cancer Center, The Northwestern Brain Tumor Institute, Northwestern University, Chicago, IL, USA.
International Institute for Nanotechnology, Northwestern University, Evanston, IL, USA.
Methods Mol Biol. 2019;1974:371-391. doi: 10.1007/978-1-4939-9220-1_25.
Spherical nucleic acids (SNAs), an emerging class of gene-regulatory nanotherapeutics, typically consist of a nanoparticle core densely functionalized with a shell of radially oriented small interfering RNA (siRNA) oligonucleotides, microRNA (miRNA) mimics, or antagonists. The unique three-dimensional SNA structure regardless of core type (e.g., gold or lipids) confers heightened resistance to nuclease-mediated degradation and accounts for robust cell entry in the absence of auxiliary transfection vehicles. In murine models of glioblastoma (GBM), the most aggressive and prevalent form of malignant brain cancers, systemically administered siRNA or miRNA-conjugated SNAs penetrated blood-brain and blood-tumor barriers and robustly reduced tumor progression. Here, we describe methods for the synthesis and physicochemical and biological characterization of SNA gene silencing effects in glioma cells in vitro and in patient-derived xenograft models in vivo.
球形核酸（SNA）是一类新兴的基因调控纳米治疗药物，通常由一个纳米颗粒核心组成，该核心被一层径向排列的小干扰RNA（siRNA）寡核苷酸、微小RNA（miRNA）模拟物或拮抗剂密集功能化。无论核心类型（如金或脂质）如何，独特的三维SNA结构都能增强对核酸酶介导降解的抵抗力，并解释了在没有辅助转染载体的情况下细胞能够有效进入的原因。在胶质母细胞瘤（GBM）的小鼠模型中，GBM是最具侵袭性和最常见的恶性脑癌形式，全身给药的siRNA或miRNA偶联的SNA能够穿透血脑屏障和血肿瘤屏障，并显著降低肿瘤进展。在这里，我们描述了在体外胶质瘤细胞和体内患者来源的异种移植模型中合成SNA基因沉默效应并进行物理化学和生物学表征的方法。
