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WIREs Nanomed Nanobiotechnol
Impact Factor: 6.14

Tuning the size, shape and structure of RNA nanoparticles for favorable cancer targeting and immunostimulation

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Abstract The past decade has shown exponential growth in the field of RNA nanotechnology. The rapid advances of using RNA nanoparticles for biomedical applications, especially targeted cancer therapy, suggest its potential as a new generation of drug. After the first milestone of small molecule drugs and the second milestone of antibody drugs, it was predicted that RNA drugs, either RNA itself or chemicals/ligands that target RNA, will be the third milestone in drug development. Thus, a comprehensive assessment of the current therapeutic RNA nanoparticles is urgently needed to meet the drug evaluation criteria. Specifically, the pharmacological and immunological profiles of RNA nanoparticles need to be systematically studied to provide insights in rational design of RNA‐based therapeutics. By virtue of its programmability and biocompatibility, RNA molecules can be designed to construct sophisticated nanoparticles with versatile functions/applications and highly tunable physicochemical properties. This intrinsic characteristic allows the systemic study of the effects of various properties of RNA nanoparticles on their in vivo behaviors such as cancer targeting and immune responses. This review will focus on the recent progress of RNA nanoparticles in cancer targeting, and summarize the effects of common physicochemical properties such as size and shape on the RNA nanoparticles' biodistribution and immunostimulation profiles. This article is categorized under: Biology‐Inspired Nanomaterials > Nucleic Acid‐Based Structures Diagnostic Tools > in vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Specific cancer targeting in vivo of RNA nanoparticles to (a) brain cancer (Reprinted with permission from Lee et al., ). Copyright 2015 Impact Journals; (b) breast cancer (Reprinted with permission from Shu et al. (). Copyright 2015 American Chemical Society); (c) gastric cancer (Reprinted with permission from Cui et al. (). Copyright 2015 Macmillan Publishers Limited); (d) prostate cancer (Reprinted with permission from Binzel et al. (). Copyright 2016 Elsevier Inc.); (e) colorectal cancer (Reprinted with permission from Rychahou et al. (); Xu, Pang, et al. (). Copyright 2015 American Chemical Society & Elsevier B.V).; (f) Head & Neck cancer (Reprinted with permission from Shu, Haque, et al. (). Copyright 2013 RNA society); (g) specific cancer targeting of RNA/EVs (Reprinted with permission from Pi et al. (). Copyright 2018 Springer Nature Publishing), and (h) RNA micelles (Reprinted with permission from Shu et al. ()). Copyright 2018 Elsevier Inc)
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Construction of RNA nanoparticles with various surface characteristics. (a) pRNA‐3WJ nanoparticles conjugated with hydrophobic fluorophores and their effects on in vivo biodistribution (Reprinted with permission from Jasinski, Yin, et al. (). Copyright 2018, Mary Ann Liebert, Inc). (b) RNA micelles assembled from pRNA‐3WJ conjugated with cholesterol, paclitaxel and fluorophore (Reprinted with permission from Shu et al. (). Copyright 2018 Elsevier Inc). (c) Ligand‐displaying extracellular vesicles by pRNA‐3WJ conjugated with cholesterol, ligand aptamer, and fluorophore (Reprinted with permission from Pi et al. (). Copyright 2018 Springer Nature Publishing)
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Effects of RNA nanoparticles' physicochemical properties on immunostimulation. RNA nanoparticles with (a) varying size, (b) varying shape, (c) different stoichiometry, (d) different sequence, and (e) different dimension induced cytokines and interferons secretion to various levels. (figures A‐D and E reprinted with permission from Guo et al. (). Copyright 2018 Elsevier Inc). and (Reprinted with permission from Hong et al. (). Copyright 2018 American Chemical Society, respectively)
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Effects of RNA nanoparticle size and shape on in vivo biodistribution. (a) RNA squares with identical shape but varying size, and (b) RNA polygons with identical size but varying shape show different circulation times and tumor accumulation in vivo. (Reprinted with permission from Jasinski, Li, and Guo (). Copyright 2018 Elsevier Inc.)
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Construction of RNA nanostructures with tunable properties. (a) RNA squares with small, medium, and large size by tuning the length of the connecting helix (Reprinted with permission from Jasinski et al. (). Copyright 2014 American Chemical Society). (b) RNA triangle, square and pentagon by tuning the interior pRNA‐3WJ angle (Reprinted with permission from Khisamutdinov, Li, et al. (). Copyright 2014 American Chemical Society). (c) 3D RNA cube, planar RNA nanoring, and linear RNA fiber by different connectivity (Reprinted with permission from Hong et al. (). Copyright 2018 American Chemical Society)
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Modular design and construction of RNA nanostructures. (a) pRNA hexamer from phi29 DNA packaging motor (Reprinted with permission from Shu, Haque, et al. (). Copyright 2013 RNA society); (b) RNA square with tectoRNA motif (Reprinted with permission from Chworos et al. (). Copyright 2004 The American Association for the Advancement of Science); (c) RNA triangle with IIa motif from SVV IRES (Reprinted with permission from Boerneke et al. ()). Copyright 2016 John Wiley & Sons, Inc.) & RNA square with IIa‐1 motif from HCV (Reprinted with permission from Dibrov et al. (). Copyright 2011 National Academy of Sciences; (d) RNA triangle and square with k‐turn motif (Reprinted with permission from Huang and Lilley (). Copyright 2016 The Royal Society of Chemistry); (e) RNA triangle with tetra‐U motif (Reprinted with permission from Bui et al. (). Copyright 2017 Elsevier Inc).; (f) RNA‐protein triangle with k‐turn motif (Reprinted with permission from Ohno et al. (). Copyright 2011 Nature Publishing Group); (g) RNA tectosquare with RA, 3WJ, and tRNA motifs (Reprinted with permission from Severcan et al. (). Copyright 2009 American Chemical Society); (h) RNA nanoring based on RNAI/II inverse kissing complex (Reprinted with permission from Grabow et al. (). Copyright 2011 American Chemical Society); (i) RNA cube designed in silico (Reprinted with permission from Afonin et al. (). Copyright 2010 Macmillan Publishers Limited); (j) pRNA‐3WJ motif‐based RNA tetrahedron (Reprinted with permission from Li et al. (). Copyright 2016 John Wiley & Sons, Inc.), pyramid (Reprinted with permission from Xu C et al. (2018). Copyright 2018 Springer Nature), & nanoprism (Reprinted with permission from Khisamutdinov et al. ()). Copyright 2016 John Wiley & Sons, Inc.); (k) RNA polyhedron made of tRNA subunit (Reprinted with permission from Severcan et al. (). Copyright 2010 Macmillan Publishers Limited); (l) triangular and tetragonal RNA prism from re‐engineered pRNA (Reprinted with permission from Hao et al. (). Copyright 2014 Macmillan Publishers Limited); (m) homo‐octameric RNA prism with T‐junction RNA tile (Reprinted with permission from Yu et al. (). Copyright 2015 Macmillan Publishers Limited); (n) RNA dendrimers from pRNA‐3WJ motif (Reprinted with permission from Sharma et al. (). Copyright 2015 Elsevier Inc.); (o) RNA nanoheart from a syntax of RNA modules (Reprinted with permission from Geary et al. ()). Copyright 2017 American Chemical Society
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Diagnostic Tools > In Vivo Nanodiagnostics and Imaging
Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
Biology-Inspired Nanomaterials > Nucleic Acid-Based Structures

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