DNA‐Driven Two‐Layer Core–Satellite Gold Nanostructures for Ultrasensitive MicroRNA Detection in Living Cells

Abstract

It is a significant challenge to achieve controllable self‐assembly of superstructures for biological applications in living cells. Here, a two‐layer core–satellite assembly is driven by a Y‐DNA, which is designed with three nucleotide chains that hybridized through complementary sequences. The two‐layer core–satellite nanostructure (C30S5S10 NS) is constructed using 30 nm gold nanoparticles (Au NPs) as the core, 5 nm Au NPs as the first satellite layer, and 10 nm Au NPs as the second satellite layer, resulting in a very strong circular dichroism (CD) and surface‐enhanced Raman scattering. After optimization, the yield is up to 85%, and produces a g‐factor of 0.16 × 10−2. The hybridization of the target microRNA (miRNA) with the molecular probe causes a significant drop in the CD and Raman signals, and this phenomenon is used to detect the miRNA in living cells. The CD signal has a good linear range of 0.011–20.94 amol ngRNA−1 and a limit of detection (LOD) of 0.0051 amol ngRNA−1, while Raman signal with the range of 0.052–34.98 amol ngRNA−1 and an LOD of 2.81 × 10−2 amol ngRNA−1. This innovative dual‐signal method can be used to quantify biomolecules in living cells, opening the way for ultrasensitive, highly accurate, and reliable diagnoses of clinical diseases.

Shining light on chiral inorganic nanomaterials for biological issues

“…Similarly, for biomarker detections, Kuang's group 140 has also reported a chiral Au-based double-layer core-satellite nanostructure, which is construct by the self-assembly strategy and based on Y-DNA hybridization (CAM) (Figure 9 H). The nanostructure (C 30 S 5 S 10 NS) was constructed by using 30 nm gold nanoparticles (Au NPs) as the core, 5 nm Au NPs as the first satellite layer, and 10 nm Au NPs as the second satellite layer, resulting in very strong CD signals and surface-enhanced Raman scattering.…”

“…Panel G is adapted with permission from 139 , copyright 2017 Wiley-VCH. Panel H is adapted with permission from 140 , copyright 2020 Wiley-VCH. Panel I is adapted with permission from 141 , copyright 2017 the Royal Society of Chemistry.…”

Synthesis of SERS-active core–satellite nanoparticles using heterobifunctional PEG linkers

“…While smaller inorganic nanoparticles such as gold, silver, or semiconductor NPs as satellites are explored. The nano spacer linkers that are commonly employed include (1) protein based assembly 41 , (2) polymeric based assembly [42][43][44] , (3) DNA -assisted assembly 36, [45][46][47][48][49] , and (4) molecular linkers that directly bridge the plasmonic units using either covalent or electrostatic interactions of the functional groups 37,50-52 . For example, Chen et al demonstrated the synthesis of streptavidin-coated polymeric bead core -Au satellite assembly via DNA linkers 53 .…”

Research Progress on Surface-Enhanced Raman Spectroscopy Technique for the Detection of microRNA

“…Figure 1 Schematic illustration of a synergistic calibrated SERS strategy for the detection of cancer-related microRNA-182 [17] Yuan 等 [19] [20] . Xiao 等 [21] [22] 还构建了一种基于 DSN 技术的功能性 [19] Figure 2 Schematic for SERS biosensor based on Fe 3 O 4 @PDA/Pt and DSN signal amplification for microRNA-155 detection [19] 基于 [25] ; (B) CuPc@HG@BN 探针的构建与其用于诊疗一体化的示意图 [26] Figure 3 (A) Schematic representation of Y-DNA-driven construction of Au NP chiral C 30 S 5 S 10 NSs with enhanced CD and SERS signals for the detection of microRNA in tumor cell [25] ; (B) illustration of the synthesis of CuPc@HG@BN probe and the antitumor and SERS monitoring mechanism [26] microRNA-21 的高灵敏和高准确的监测及光动力治疗, 如图 3B 所示, AS1141 修饰的发卡探针(HG1 和 HG2)负 载于酞菁铜(CuPc)上形成 CuPc@HG, 然后通过 π-π 作用 将 CuPc@HG 固定于六方氮化硼纳米片(h-BNNS)上构 [27] Figure 4 Schematic of DNA-mediated gold-silver nano-mushrooms as SERS probes for ultrasensitive and multiplex DNA/miRNA detection [27] Liu 课题组 [33] [33] Figure 5 Schematic of the AgNP dimer probes and the protocol for microRNA-21 detection with the in situ hot-spot assembly strategy [33] 化 学 学 报 [37] [36] Figure 6 Schematic of the optical sensor based on target mi-croRNA-directed formation of AuNR chiral side-by-side dimers for the detection of intracellular microRNA [36] Ye 研究小组 [40] [47] 构建基于分支 DNA 的"三明治"SERS 传感平台用于高灵敏检测血清中 microRNA 和 α-胎蛋白, 用于肝癌的早期诊断, 该方法 对 microRNA 和 α-胎蛋白的检测限分别为 10 amol/L 和 10 −12 mol/L. Cao 课题组 [48]…”

“…Xu 等[25] 设计了一种 Y 型 DNA 驱动的双层核壳金纳米结构(C 30 S 5 S 10 NS)作为 双信号分子探针, 该探针同时具有很强的圆二色性(CD) 与 SERS 信号, 其检测原理如图 3A 所示: 当肿瘤细胞内 目标 microRNA 与 Y 型 DNA 中的目标识别 DNA (DNA RT )杂交后, 导致 C 30 S 5 S 10 NS 解离, 相应地使 CD 和 SERS 信号减小, CD 对目标 microRNA 的检测限为…”