核酸
DNA
纳米技术
细胞
纳米结构
生物物理学
材料科学
化学
细胞生物学
生物化学
生物
作者
Ana S. G. Martins,Sara Reis,Erik Benson,Marco M. Domingues,João Cortinhas,Joana Silva,Sofia Duque Santos,Nuno C. Santos,Ana Paula Pêgo,Pedro M. D. Moreno
出处
期刊:Small
[Wiley]
日期:2024-02-11
标识
DOI:10.1002/smll.202309140
摘要
Abstract The successful translation of therapeutic nucleic acids (NAs) for the treatment of neurological disorders depends on their safe and efficient delivery to neural cells, in particular neurons. DNA nanostructures can be a promising NAs delivery vehicle. Nonetheless, the potential of DNA nanostructures for neuronal cell delivery of therapeutic NAs is unexplored. Here, tetrahedral DNA nanostructures (TDN) as siRNA delivery scaffolds to neuronal cells, exploring the influence of functionalization with two different reported neuronal targeting ligands: C4‐3 RNA aptamer and Tet1 peptide are investigated. Nanostructures are characterized in vitro, as well as in silico using molecular dynamic simulations to better understand the overall TDN structural stability. Enhancement of neuronal cell uptake of TDN functionalized with the C4‐3 Aptamer (TDN‐Apt), not only in neuronal cell lines but also in primary neuronal cell cultures is demonstrated. Additionally, TDN and TDN‐Apt nanostructures carrying siRNA are shown to promote silencing in a process aided by chloroquine‐induced endosomal disruption. This work presents a thorough workflow for the structural and functional characterization of the proposed TDN as a nano‐scaffold for neuronal delivery of therapeutic NAs and for targeting ligands evaluation, contributing to the future development of new neuronal drug delivery systems based on DNA nanostructures.
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