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载体和配体空间构象对 RNA 纳米药物细胞递送的影响。

The Effects of the Carrier and Ligand Spatial Conformation on RNA Nanodrug Cell Delivery.

机构信息

School of Chemistry and Life Science, Advanced Institute of Materials Science, Changchun University of Technology, Changchun 130012, China.

State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.

出版信息

Anal Chem. 2024 Aug 13;96(32):13226-13233. doi: 10.1021/acs.analchem.4c02270. Epub 2024 Aug 3.

DOI:10.1021/acs.analchem.4c02270
PMID:39096242
Abstract

Small interfering RNA (siRNA) highlights the immense therapeutic potential for cancer treatment. The major challenge in siRNA therapy is the effective RNA nanodrug delivery system, which is facilitated by the ligand and the carrier. In this study, we analyzed the binding specificity of linear RGD and circular RGD to αβ integrins by mapping the morphology using super-resolution direct stochastic optical reconstruction microscopy. Meanwhile, the binding dynamics was investigated using single-molecule force spectroscopy. Then, the effects of the ligand and carrier on RNA nanodrug cell entry dynamic parameters were evaluated at the single particle level by the force tracing technique. Furthermore, the delivery efficiency of RNA nanodrugs was assessed using AFM-based nanoindentation at the single cell level. This report will provide valuable insights for rational design strategies aiming to achieve improved efficiency for nanodrug delivery systems.

摘要

小干扰 RNA(siRNA)突出了癌症治疗的巨大治疗潜力。siRNA 治疗的主要挑战是有效的 RNA 纳米药物递送系统,这得益于配体和载体。在这项研究中,我们通过使用超分辨率直接随机光学重建显微镜绘制形态图来分析线性 RGD 和环状 RGD 与 αβ 整联蛋白的结合特异性。同时,使用单分子力谱法研究了结合动力学。然后,通过力跟踪技术在单个颗粒水平上评估了配体和载体对 RNA 纳米药物细胞进入动力学参数的影响。此外,还使用基于原子力显微镜的纳米压痕在单细胞水平上评估了 RNA 纳米药物的递送效率。本报告将为旨在提高纳米药物递送系统效率的合理设计策略提供有价值的见解。

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