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WIREs Nanomed Nanobiotechnol
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In vivo imaging of the systemic delivery of small interfering RNA

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Abstract Short interfering RNAs (siRNAs) have emerged as a potent new class of therapeutics, which regulate gene expression through sequence‐specific inhibition of mRNA translation. Human trials of siRNAs have highlighted the need for robust delivery and detection techniques that will enable the application of these therapeutics to increasingly complex disease and organ systems. Efforts to monitor the in vivo trafficking and efficacy of siRNAs have routinely involved bioluminescence imaging of naked siRNA molecules. More recently, siRNAs have been incorporated into a variety of molecular imaging probes to promote their detection with clinically relevant imaging modalities. Lipid‐, polymer‐, and nanoparticle‐based siRNA delivery vehicles have proven effective in improving the stability, bioavailability, and target specificity of siRNAs following systemic administration in vivo. Additionally, these methods provide a platform to modify siRNAs with a variety of contrast agents and have enabled nuclear and magnetic resonance imaging of siRNA delivery in preclinical studies. These image‐guided delivery approaches represent a crucial step in the transition of siRNA therapeutics to the clinic. WIREs Nanomed Nanobiotechnol 2012, 4:428–437. doi: 10.1002/wnan.1158 This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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Multimodality imaging of near infrared (NIR)‐labeled iron oxide nanoparticle (MN‐NIRF‐siGFP) delivery to tumors. Accumulation of MN‐NIRF‐siGFP in 9L‐GFP and 9L‐RFP bilateral tumors was confirmed by both magnetic resonance and optical imaging. MN‐NIRF‐siGFP delivery was reflected by decreased T2 relaxation in magnetic resonance (MR) images (a) and by the emergence of high intensity NIR signal in whole‐body optical images (b) 24 h after probe administration. (Reprinted with permission from Ref 49. Copyright 2007 Macmillan Publishers Ltd.)

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Tumor‐targeted siRNA delivery with iron oxide nanoparticles (MN‐EPPT‐siBIRC5). (a) T2 MR images and T2 maps of mice bearing human breast adenocarcinoma tumors showed decreased signal intensity and T2 shortening in tumors following intravenous injection of MN‐EPPT‐siBIRC5, indicating accumulation of probe. (b) MN‐EPPT‐siBIRC5 accumulation was associated with a fivefold increase in apoptosis induction relative to scrambled control siRNA (MN‐EPPT‐siSCR) probes (P = 0.003). (c) MN‐EPPT‐siBIRC5 also led to a twofold reduction in tumor growth rate relative to controls eight days after treatment (P < 0.01). (Reprinted with permission from Ref 50. Copyright 2010 AACR)

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Efficacy of siGFP delivered with iron oxide nanoparticles. (a) MN‐NIRF‐siGFP delivery resulted in reduction of 9L‐GFP tumor fluorescence 48 h after probe administration. No reduction of 9L‐RFP fluorescence was observed, indicating that silencing by MN‐NIRF‐siGFP was gene specific. (b) Suppression of green fluorescent protein (GFP) expression by MN‐NIRF‐siGFP was confirmed by quantitative reverse transcription polymerase chain reaction (RT‐PCR) analysis of RNA extracted from 9L‐GFP tumors. Treatment reduced gfp mRNA levels by 85% and 97% relative to saline‐treated and mismatch scrambled control siRNA probes, respectively (P < 0.001). (Reprinted with permission from Ref 49. Copyright 2007 Macmillan Publishers Ltd.)

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Therapeutic Approaches and Drug Discovery > Emerging Technologies
Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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