RNA Delivery via DNA-Inspired Janus Base Nanotubes for Extracellular Matrix Penetration

RNA Delivery via DNA-Inspired Janus Base Nanotubes for Extracellular Matrix Penetration
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DOI:
10.1557/adv.2020.47
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发表时间:
2020-01-01
期刊:
影响因子:
0.8
通讯作者:
Chen Yupeng
Chen Yupeng
中科院分区:
其他
文献类型:
--
作者:
Sands, Ian;Lee, Jinhyung;Chen Yupeng

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RNA递送到具有致密细胞外基质(ECM)的深层组织中一直具有挑战性。例如,软骨由于其无血管结构、低细胞密度和强负表面电荷而成为RNA和药物递送的主要屏障。软骨细胞外基质由胶原、蛋白多糖和其他各种非胶原蛋白组成,间距为20 nm。传统的纳米颗粒通常是球形的,直径大于50- 60 nm(负载货物后)。因此,他们在RNA递送到软骨中方面取得了有限的成功。在这里,我们开发了Janus碱基纳米管(JBNT,自组装纳米管,灵感来自DNA碱基对)与小RNA组装形成纳米棒传递载体(称为“纳米片”)。纳米片的直径近似于20 nm(货物装载后的最小运载工具),长度近似于100 nm。由于尺寸减小和可调节的特性,它们在ECM渗透方面呈现了新的突破,以促进ECM和细胞内渗透。
RNA delivery into deep tissues with dense extracellular matrix (ECM) has been challenging. For example, cartilage is a major barrier for RNA and drug delivery due to its avascular structure, low cell density and strong negative surface charge. Cartilage ECM is comprised of collagens, proteoglycans, and various other noncollagneous proteins with a spacing of 20nm. Conventional nanoparticles are usually spherical with a diameter larger than 50-60nm (after cargo loading). Therefore, they presented limited success for RNA delivery into cartilage. Here, we developed Janus base nanotubes (JBNTs, self-assembled nanotubes inspired from DNA base pairs) to assemble with small RNAs to form nano-rod delivery vehicles (termed as "Nanopieces"). Nanopieces have a diameter of similar to 20nm (smallest delivery vehicles after cargo loading) and a length of similar to 100nm. They present a novel breakthrough in ECM penetration due to the reduced size and adjustable characteristics to encourage ECM and intracellular penetration.