Non-Cationic RGD-Containing Protein Nanocarrier for Tumor-Targeted siRNA Delivery

Despite the recent successes in siRNA therapeutics, targeted delivery beyond the liver remains the major hurdle for the widespread application of siRNA in vivo. Current cationic liposome or polymer-based delivery agents are restricted to the liver and suffer from off-target effects, poor clearance,...

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Main Authors: Xiaolin Yu (Author), Lu Xue (Author), Jing Zhao (Author), Shuhua Zhao (Author), Daqing Wu (Author), Hong Yan Liu (Author)
Format: Book
Published: MDPI AG, 2021-12-01T00:00:00Z.
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042 |a dc 
100 1 0 |a Xiaolin Yu  |e author 
700 1 0 |a Lu Xue  |e author 
700 1 0 |a Jing Zhao  |e author 
700 1 0 |a Shuhua Zhao  |e author 
700 1 0 |a Daqing Wu  |e author 
700 1 0 |a Hong Yan Liu  |e author 
245 0 0 |a Non-Cationic RGD-Containing Protein Nanocarrier for Tumor-Targeted siRNA Delivery 
260 |b MDPI AG,   |c 2021-12-01T00:00:00Z. 
500 |a 10.3390/pharmaceutics13122182 
500 |a 1999-4923 
520 |a Despite the recent successes in siRNA therapeutics, targeted delivery beyond the liver remains the major hurdle for the widespread application of siRNA in vivo. Current cationic liposome or polymer-based delivery agents are restricted to the liver and suffer from off-target effects, poor clearance, low serum stability, and high toxicity. In this study, we genetically engineered a non-cationic non-viral tumor-targeted universal siRNA nanocarrier (MW 26 KDa). This protein nanocarrier consists of three function domains: a dsRNA binding domain (dsRBD) (from human protein kinase R) for any siRNA binding, 18-histidine for endosome escape, and two RGD peptides at the N- and C-termini for targeting tumor and tumor neovasculature. We showed that cloned dual-RGD-dsRBD-18his (dual-RGD) protein protects siRNA against RNases, induces effective siRNA endosomal escape, specifically targets integrin α<sub>v</sub>β<sub>3</sub> expressing cells in vitro, and homes siRNA to tumors in vivo. The delivered siRNA leads to target gene knockdown in the cell lines and tumor xenografts with low toxicity. This multifunctional and biomimetic siRNA carrier is biodegradable, has low toxicity, is suitable for mass production by fermentation, and is serum stable, holding great potential to provide a widely applicable siRNA carrier for tumor-targeted siRNA delivery. 
546 |a EN 
690 |a RGD 
690 |a siRNA delivery 
690 |a tumor targeting 
690 |a tumor neo-vasculature 
690 |a integrin α<sub>v</sub>β<sub>3</sub> 
690 |a dsRNA binding domain 
690 |a Pharmacy and materia medica 
690 |a RS1-441 
655 7 |a article  |2 local 
786 0 |n Pharmaceutics, Vol 13, Iss 12, p 2182 (2021) 
787 0 |n https://www.mdpi.com/1999-4923/13/12/2182 
787 0 |n https://doaj.org/toc/1999-4923 
856 4 1 |u https://doaj.org/article/06339cacadf74e7c8f96d4b7a1d0d85b  |z Connect to this object online.