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WIREs Nanomed Nanobiotechnol
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Bioengineered nanoparticles for siRNA delivery

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Short interfering RNA (siRNA) has been an important laboratory tool in the last two decades and has allowed researchers to better understand the functions of nonprotein‐coding genes through RNA interference (RNAi). Although RNAi holds great promise for this purpose as well as for treatment of many diseases, efforts at using siRNA have been hampered by the difficulty of safely and effectively introducing it into cells of interest, both in vitro and in vivo. To overcome this challenge, many biomaterials and nanoparticles (NPs) have been developed and optimized for siRNA delivery, often taking cues from the DNA delivery field, although different barriers exist for these two types of molecules. In this review, we discuss general properties of biomaterials and nanoparticles that are necessary for effective nucleic acid delivery. We also discuss specific examples of bioengineered materials, including lipid‐based NPs, polymeric NPs, inorganic NPs, and RNA‐based NPs, which clearly illustrate the problems and successes in siRNA delivery. WIREs Nanomed Nanobiotechnol 2013. doi: 10.1002/wnan.1233 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease

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siRNA faces several barriers during intracellular delivery. Representative biomaterials that are able to overcome these barriers are shown above, along with the particular strategy employed by that material.
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PLGA‐b‐PLL‐g‐PEG NPs contain siRNA, two drugs, and three ligands for targeting, cell penetration, and trafficking. (Reprinted with permission from Ref . Copyright 2012 Elsevier)
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Widely used approaches to improving polymeric siRNA delivery include conjugation to PEG and targeting ligands (a) and introduction of disulfide bridges for controlled cytoplasmic release (b). (a: Reprinted with permission from Ref . Copyright 2012 American Chemical Society; b: Reprinted with permission from Ref . Copyright 2011 Elsevier)
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Various approaches have been taken to lipid‐based siRNA delivery. While some groups use rational design and focus on specific delivery aspects, such as lipid polymorphism leading to membrane fusion (a), others have employed high‐throughput methods to screen through a wide array of different molecules to empirically determine the best structures (b and c). (a: Reprinted with permission from Ref . Copyright 2010 Macmillan Publishers Ltd; b and c: Reprinted with permission from Ref . Copyright 2010 Macmillan Publishers Ltd)
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Examples of classes of polymeric and lipidic biomaterials used for siRNA delivery.
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Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease
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