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DNA-inspired nanomaterials for enhanced endosomal escape [Engineering]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.412 ) Pub Date : 2021-05-11 , DOI: 10.1073/pnas.2104511118
Jinhyung Lee, Ian Sands, Wuxia Zhang, Libo Zhou, Yupeng Chen

To realize RNA interference (RNAi) therapeutics, it is necessary to deliver therapeutic RNAs (such as small interfering RNA or siRNA) into cell cytoplasm. A major challenge of RNAi therapeutics is the endosomal entrapment of the delivered siRNA. In this study, we developed a family of delivery vehicles called Janus base nanopieces (NPs). They are rod-shaped nanoparticles formed by bundles of Janus base nanotubes (JBNTs) with RNA cargoes incorporated inside via charge interactions. JBNTs are formed by noncovalent interactions of small molecules consisting of a base component mimicking DNA bases and an amino acid side chain. NPs presented many advantages over conventional delivery materials. NPs efficiently entered cells via macropinocytosis similar to lipid nanoparticles while presenting much better endosomal escape ability than lipid nanoparticles; NPs escaped from endosomes via a “proton sponge” effect similar to cationic polymers while presenting significant lower cytotoxicity compared to polymers and lipids due to their noncovalent structures and DNA-mimicking chemistry. In a proof-of-concept experiment, we have shown that NPs are promising candidates for antiviral delivery applications, which may be used for conditions such as COVID-19 in the future.



中文翻译:

DNA启发的纳米材料可增强内体逃逸[工程学]

为了实现RNA干扰(RNAi)治疗,必须将治疗性RNA(例如小干扰RNA或siRNA)递送到细胞质中。RNAi治疗的主要挑战是所递送的siRNA的内体包裹。在这项研究中,我们开发了一系列称为Janus base nanopieces(NPs)的运载工具。它们是棒状纳米颗粒,由Janus基础纳米管(JBNT)束与通过电荷相互作用掺入其中的RNA货物形成。JBNT由小分子的非共价相互作用形成,该小分子由模仿DNA碱基和氨基酸侧链的碱基组成。与传统的传递材料相比,NP具有许多优势。NPs通过类似于脂类纳米颗粒的巨胞饮作用有效进入细胞,同时具有比脂质纳米颗粒更好的内体逃逸能力。NPs通过类似于阳离子聚合物的“质子海绵”效应从内体逃逸,但由于其非共价结构和模拟DNA的化学性质,与聚合物和脂质相比,其细胞毒性显着降低。在概念验证实验中,我们表明NP是抗病毒递送应用的有前途的候选者,将来可能会用于诸如COVID-19的条件。

更新日期:2021-05-03
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