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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MDPI AG,
2021-12-01T00:00:00Z.
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LEADER | 00000 am a22000003u 4500 | ||
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001 | doaj_06339cacadf74e7c8f96d4b7a1d0d85b | ||
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. |