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DOI10.1038/s41467-017-00912-x
In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers
Watanabe, Sumiyo1,2,3; Hayashi, Kotaro4; Toh, Kazuko4; Kim, Hyun Jin1; Liu, Xueying4; Chaya, Hiroyuki1,5; Fukushima, Shigeto4; Katsushima, Keisuke6; Kondo, Yutaka6; Uchida, Satoshi7; Ogura, Satomi4,5; Nomoto, Takahiro8; Takemoto, Hiroyasu8; Cabral, Horacio7; Kinoh, Hiroaki4; Tanaka, Hiroyoshi Y.9; Kano, Mitsunobu R.9,10; Matsumoto, Yu1; Fukuhara, Hiroshi11; Uchida, Shunya2; Nangaku, Masaomi3; Osada, Kensuke7; Nishiyama, Nobuhiro8; Miyata, Kanjiro1,5; Kataoka, Kazunori4,12
2019-04-24
发表期刊NATURE COMMUNICATIONS
ISSN2041-1723
出版年2019
卷号10
文章类型Article
语种英语
国家Japan
英文摘要

Stabilisation of fragile oligonucleotides, typically small interfering RNA (siRNA), is one of the most critical issues for oligonucleotide therapeutics. Many previous studies encapsulated oligonucleotides into similar to 100-nm nanoparticles. However, such nanoparticles inevitably accumulate in liver and spleen. Further, some intractable cancers, e.g., tumours in pancreas and brain, have inherent barrier characteristics preventing the penetration of such nanoparticles into tumour microenvironments. Herein, we report an alternative approach to cancer-targeted oligonucleotide delivery using a Y-shaped block catiomer (YBC) with precisely regulated chain length. Notably, the number of positive charges in YBC is adjusted to match that of negative charges in each oligonucleotide strand (i.e., 20). The YBC rendezvouses with a single oligonucleotide in the bloodstream to generate a dynamic ion-pair, termed unit polyion complex (uPIC). Owing to both significant longevity in the bloodstream and appreciably small size (similar to 18 nm), the uPIC efficiently delivers oligonucleotides into pancreatic tumour and brain tumour models, exerting significant antitumour activity.


领域资源环境
收录类别SCI-E
WOS记录号WOS:000465368500001
WOS关键词POLYMERIC MICELLES ; RNA INTERFERENCE ; SIRNA ; TUMORS ; ACCUMULATION ; THERAPEUTICS ; DELIVERY ; CELL ; MACROMOLECULES ; MECHANISM
WOS类目Multidisciplinary Sciences
WOS研究方向Science & Technology - Other Topics
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文献类型期刊论文
条目标识符http://119.78.100.173/C666/handle/2XK7JSWQ/203449
专题资源环境科学
作者单位1.Univ Tokyo, Ctr Dis Biol & Integrat Med, Grad Sch Med, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan;
2.Teikyo Univ, Dept Internal Med, Div Nephrol, Sch Med,Itabashi Ku, 2-11-1 Kaga, Tokyo 1738605, Japan;
3.Univ Tokyo, Grad Sch Med, Div Nephrol & Endocrinol, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138544, Japan;
4.Kawasaki Inst Ind Promot, Innovat Ctr NanoMed, Kawasaki Ku, 3-25-14 Tonomachi, Kawasaki, Kanagawa 2100821, Japan;
5.Univ Tokyo, Grad Sch Engn, Dept Mat Engn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan;
6.Nagoya Univ, Div Canc Biol, Grad Sch Med, Showa Ku, 65 Tsurumai Cho, Nagoya, Aichi 4668550, Japan;
7.Univ Tokyo, Grad Sch Engn, Dept Bioengn, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138656, Japan;
8.Tokyo Inst Technol, Inst Innovat Res, Lab Chem & Life Sci, Midori Ku, R1-11,4259 Nagatsuta, Yokohama, Kanagawa 2268503, Japan;
9.Okayama Univ, Dept Pharmaceut Biomed, Grad Sch Med Dent & Pharmaceut Sci, Kita Ku, 1-1-1 Tsushima Naka, Okayama, Okayama 7008530, Japan;
10.Okayama Univ, Dept Pharmaceut Biomed, Grad Sch Interdisciplinary Sci & Engn Hlth Syst, Kita Ku, 1-1-1 Tsushima Naka, Okayama, Okayama 7008530, Japan;
11.Kyorin Univ, Dept Urol, Fac Med, 6-20-2 Shinkawa, Mitaka, Tokyo 1818611, Japan;
12.Univ Tokyo, Inst Future Initiat, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1130033, Japan
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Watanabe, Sumiyo,Hayashi, Kotaro,Toh, Kazuko,et al. In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers[J]. NATURE COMMUNICATIONS,2019,10.
APA Watanabe, Sumiyo.,Hayashi, Kotaro.,Toh, Kazuko.,Kim, Hyun Jin.,Liu, Xueying.,...&Kataoka, Kazunori.(2019).In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers.NATURE COMMUNICATIONS,10.
MLA Watanabe, Sumiyo,et al."In vivo rendezvous of small nucleic acid drugs with charge-matched block catiomers to target cancers".NATURE COMMUNICATIONS 10(2019).
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