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RNA Nanoparticles as Rubber for Compelling Vessel Extravasation to Enhance Tumor Targeting and for Fast Renal Excretion to Reduce Toxicity.
ACS Nano ( IF 15.8 ) Pub Date : 2020-09-09 , DOI: 10.1021/acsnano.0c04863
Chiran Ghimire 1 , Hongzhi Wang 1 , Hui Li 1 , Mario Vieweger 1 , Congcong Xu 1 , Peixuan Guo 1
Affiliation  

Rubber is a fascinating material in both industry and daily life. The development of elastomeric material in nanotechnology is imperative due to its economic and technological potential. By virtue of their distinctive physicochemical properties, nucleic acids have been extensively explored in material science. The Phi29 DNA packaging motor contains a 3WJ with three angles of 97°, 125°, and 138°. Here, the rubber-like property of RNA architectures was investigated using optical tweezers and in vivo imaging technologies. The 3WJ 97° interior angle was contracted or stretched to 60°, 90°, and 108° at will to build elegant RNA triangles, squares, pentagons, cubes, tetrahedrons, dendrimers, and prisms. RNA nanoarchitecture was stretchable and shrinkable by optical tweezer with multiple extension and relaxation repeats like a rubber. Comparing to gold and iron nanoparticles with the same size, RNA nanoparticles display stronger cancer-targeting outcomes, while less accumulation in healthy organs. Generally, the upper limit of renal excretion is 5.5 nm; however, the 5, 10, and 20 nm RNA nanoparticles passed the renal filtration and resumed their original structure identified in urine. These findings solve two previous mysteries: (1) Why RNA nanoparticles have an unusually high tumor targeting efficiency since their rubber or amoeba-like deformation property enables them to squeeze out of the leaky vasculature to improve the EPR effect; and (2) why RNA nanoparticles remain non-toxic since they can be rapidly cleared from the body via renal excretion into urine with little accumulation in the body. Considering its controllable shape and size plus its rubber-like property, RNA holds great promises for industrial and biomedical applications especially in cancer therapeutics delivery.

中文翻译:


RNA 纳米颗粒作为橡胶,可迫使血管外渗以增强肿瘤靶向性,并用于快速肾排泄以降低毒性。



橡胶在工业和日常生活中都是一种令人着迷的材料。由于其经济和技术潜力,纳米技术中弹性材料的发展势在必行。凭借其独特的理化性质,核酸在材料科学中得到了广泛的探索。 Phi29 DNA 包装电机包含一个 3WJ,具有 97°、125° 和 138° 三个角度。在这里,使用光镊和体内成像技术研究了 RNA 结构的橡胶样特性。 3WJ 97°内角随意收缩或拉伸至60°、90°和108°,构建优雅的RNA三角形、正方形、五边形、立方体、四面体、树枝状聚合物和棱柱。 RNA纳米结构可以通过光镊进行拉伸和收缩,像橡胶一样具有多次延伸和松弛重复。与相同尺寸的金和铁纳米粒子相比,RNA纳米粒子表现出更强的癌症靶向效果,同时在健康器官中的积累更少。一般肾排泄上限为5.5 nm;然而,5、10 和 20 nm RNA 纳米颗粒通过了肾脏过滤,并恢复了尿液中识别出的原始结构。这些发现解决了之前的两个谜团:(1)为什么RNA纳米颗粒具有异常高的肿瘤靶向效率,因为它们的橡胶或阿米巴样变形特性使它们能够从渗漏的脉管系统中挤出来提高EPR效果; (2)为什么RNA纳米颗粒保持无毒,因为它们可以通过肾脏排泄到尿液中而被迅速从体内清除,并且在体内几乎没有积累。 考虑到其可控的形状和大小以及其类似橡胶的特性,RNA 在工业和生物医学应用,特别是在癌症治疗递送方面具有广阔的前景。
更新日期:2020-10-28
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