Journal
NANO TODAY
Volume 7, Issue 4, Pages 245-257Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.nantod.2012.06.010
Keywords
Nanotechnology; Nanobiotechnology; Nanomotor; DNA packaging motor; Bacteriophage phi29; RNA nanotechnology; RNA nanoparticle; RNA therapeutics
Categories
Funding
- NIH [EB003730, CA151648]
- NIH SIG program
- UNMC Program of ENRI
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One of the advantages of nanotechnology is the feasibility to construct therapeutic particles carrying multiple therapeutics with defined structure and stoichiometry. The field of RNA nanotechnology is emerging. However, controlled assembly of stable RNA nanoparticles with multiple functionalities which retain their original role is challenging due to refolding after fusion. Herein, we report the construction of thermodynamically stable X-shaped RNA nanoparticles to carry four therapeutic RNA motifs by self-assembly of reengineered small RNA fragments. We proved that each arm of the four helices in the X-motif can harbor one siRNA, ribozyme, or aptamer without affecting the folding of the central pRNA-X core, and each daughter RNA molecule within the nanoparticle folds into their respective authentic structures and retains their biological and structural function independently. Gene silencing effects were progressively enhanced as the number of the siRNA in each pRNA-X nanoparticles gradually increased from one to two, three, and four. More importantly, systemic injection of ligand-containing nanoparticles into the tail-vein of mice revealed that the RNA nanoparticles remained intact and strongly bound to cancers without entering the liver, lung or any other organs or tissues, while remaining in cancer tissue for more than 8 h. (c) 2012 Elsevier Ltd. All rights reserved.
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