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RNA Nanoparticles as Rubber for Compelling Vessel Extravasation to Enhance Tumor Targeting and for Fast Renal Excretion to Reduce Toxicity

  • Chiran Ghimire
    Chiran Ghimire
    Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States
  • Hongzhi Wang
    Hongzhi Wang
    Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States
    More by Hongzhi Wang
  • Hui Li
    Hui Li
    Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States
    More by Hui Li
  • Mario Vieweger
    Mario Vieweger
    Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States
  • Congcong Xu
    Congcong Xu
    Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States
    More by Congcong Xu
  • , and 
  • Peixuan Guo*
    Peixuan Guo
    Center for RNA Nanobiotechnology and Nanomedicine, College of Pharmacy, College of Medicine, Dorothy M. Davis Heart and Lung Research Institute, and James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio 43210, United States
    *Email: [email protected]
    More by Peixuan Guo
Cite this: ACS Nano 2020, 14, 10, 13180–13191
Publication Date (Web):September 9, 2020
https://doi.org/10.1021/acsnano.0c04863
Copyright © 2020 American Chemical Society

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    Abstract

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    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.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsnano.0c04863.

    • Figures of structure of 6WJ nanoparticles using Swiss PDB. Tables showing the nucleic acid oligo sequence used in in vivo studies as well as in single molecule studies (PDF)

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