新規pH応答性カチオン性脂質を用いた効率的なshort interference RNA (siRNA) デリバリーシステムの開発
書誌事項
- タイトル別名
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- Development of an Efficient Short Interference RNA (siRNA) Delivery System with a New pH-Sensitive Cationic Lipid
- シンキ pH オウトウセイ カチオンセイ シシツ オ モチイタ コウリツテキ ナ short interference RNA (siRNA)デリバリー システム ノ カイハツ
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The development of a carrier for the delivery of siRNA is a factor in the realization of RNA interference (RNAi) therapeutics. Modification of siRNA carriers with polyethylene glycol, i.e., PEGylation, is a general strategy for stabilizing a particle in the blood stream and delivering it to tissue or cells. However, it is well-known that, when a carrier is modified by PEGylation, it results in a significant inhibition of both cellular uptake and the endosomal escape process. In a previous study, we reported on the development of a multifunctional envelope-type nano device (MEND) for delivering siRNA and peptide-based functional devices for overcoming the effects conferred by PEGylation and succeeded in the delivery of siRNA to tumor tissue. In this study, we noticed that the pH-sensitive property, changing from neutral to cationic in response to a decrease in pH, could avoid the inhibition caused by PEGylation and succeeded in synthesizing a pH-sensitive cationic lipid, YSK05. The YSK05-MEND had a higher fusogenicity and potency for endosomal escape than other MENDs containing conventional cationic lipids. The PEGylated YSK05-MEND induced efficient gene silencing and avoided the inhibition of endosomal escape caused by PEGylation followed by optimization of the lipid composition. Furthermore, the intratumoral injection of the PEGylated YSK05-MEND resulted in a more efficient gene silencing compared with MENDs containing conventional cationic lipids. Thus, the YSK05-MEND is a promising siRNA carrier for avoiding the inhibition in intracellular trafficking caused by PEGylation both in vitro and in vivo.<br>
収録刊行物
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- 薬学雑誌
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薬学雑誌 132 (12), 1355-1363, 2012-12-01
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390282681105572096
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- NII論文ID
- 130002489531
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- NII書誌ID
- AN00284903
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- COI
- 1:STN:280:DC%2BC3s7osl2qug%3D%3D
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- ISSN
- 13475231
- 00316903
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- NDL書誌ID
- 024129211
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- PubMed
- 23208041
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 使用不可