Inter-molecular beta-sheet structure facilitates lung-targeting siRNA   delivery

doi:10.1038/srep22731

CORC > 北京大学 > 化学与分子工程学院

	Inter-molecular beta-sheet structure facilitates lung-targeting siRNA delivery
	Zhou, Jihan ; Li, Dong ; Wen, Hao ; Zheng, Shuquan ; Su, Cuicui ; Yi, Fan ; Wang, Jue ; Liang, Zicai ; Tang, Tao ; Zhou, Demin ; Zhang, Li-He ; Liang, Dehai ; Du, Quan
刊名	SCIENTIFIC REPORTS
	2016
关键词	DRUG-DELIVERY RIGID MICROPARTICLES PULMONARY DRUG GENE DELIVERY NANOPARTICLES CANCER MICROSPHERES RETENTION KINETICS SYSTEM
DOI	10.1038/srep22731
英文摘要	Size-dependent passive targeting based on the characteristics of tissues is a basic mechanism of drug delivery. While the nanometer-sized particles are efficiently captured by the liver and spleen, the micron-sized particles are most likely entrapped within the lung owing to its unique capillary structure and physiological features. To exploit this property in lung-targeting siRNA delivery, we designed and studied a multi-domain peptide named K-beta, which was able to form inter-molecular beta-sheet structures. Results showed that K-beta peptides and siRNAs formed stable complex particles of 60 nm when mixed together. A critical property of such particles was that, after being intravenously injected into mice, they further associated into loose and micron-sized aggregates, and thus effectively entrapped within the capillaries of the lung, leading to a passive accumulation and gene-silencing. The large size aggregates can dissociate or break down by the shear stress generated by blood flow, alleviating the pulmonary embolism. Besides the lung, siRNA enrichment and targeted gene silencing were also observed in the liver. This drug delivery strategy, together with the low toxicity, biodegradability, and programmability of peptide carriers, show great potentials in vivo applications.; National Natural Science Foundation of China [21174007, 31571403, 81400842]; National High-tech R&D Program of China [2014AA021103, 2012AA022501]; Jianghai Talent Project; SCI(E); PubMed; ARTICLE; dliang@pku.edu.cn; quan.du@pku.edu.cn; 22731; 6
语种	英语
内容类型	期刊论文
源URL	[http://ir.pku.edu.cn/handle/20.500.11897/434585]
专题	化学与分子工程学院
推荐引用方式 GB/T 7714	Zhou, Jihan,Li, Dong,Wen, Hao,et al. Inter-molecular beta-sheet structure facilitates lung-targeting siRNA delivery[J]. SCIENTIFIC REPORTS,2016.
APA	Zhou, Jihan.,Li, Dong.,Wen, Hao.,Zheng, Shuquan.,Su, Cuicui.,...&Du, Quan.(2016).Inter-molecular beta-sheet structure facilitates lung-targeting siRNA delivery.SCIENTIFIC REPORTS.
MLA	Zhou, Jihan,et al."Inter-molecular beta-sheet structure facilitates lung-targeting siRNA delivery".SCIENTIFIC REPORTS (2016).