Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid

Hatakeyama, Hiroto; Akita, Hidetaka; Ito, Erika et al.

Biomaterials, 2011, 32(18), 4306-4316

Permalink : https://hdl.handle.net/2115/46196

このアイテムのアクセス数:1,577件（2026-08-18 02:26 集計）

閲覧可能ファイル 

ファイル フォーマット サイズ 閲覧回数 説明
Bio32-18_4306-4316 pdf 804 KB 2,696

論文情報

ファイル出力 EndNote Basic出力 Mendeley出力

アクセス権
open access
URI
https://hdl.handle.net/2115/46196
タイトル
Systemic delivery of siRNA to tumors using a lipid nanoparticle containing a tumor-specific cleavable PEG-lipid
著者
Hatakeyama, Hiroto ; Akita, Hidetaka ; Ito, Erika ; Hayashi, Yasuhiro ; Oishi, Motoi ; Nagasaki, Yukio ; Danev, Radostin ; Nagayama, Kuniaki ; Kaji, Noritada ; Kikuchi, Hiroshi ; Baba, Yoshinobu ; Harashima, Hideyoshi
著者名
Hatakeyama, Hiroto
著者名
Akita, Hidetaka
著者名
Ito, Erika
著者名
Hayashi, Yasuhiro
著者名
Oishi, Motoi
著者名
Nagasaki, Yukio
著者名
Danev, Radostin
著者名
Nagayama, Kuniaki
著者名
Kaji, Noritada
著者名
Kikuchi, Hiroshi
著者名
Baba, Yoshinobu
著者名
Harashima, Hideyoshi
言語
英語
キーワード
Multifunctional envelope-type nano device (MEND)
Systemic siRNA delivery
Cleavable PEG
Matrix metalloproteinase
PEG dilemma
EPR effect
発行日
2011-06
出版者
Elsevier
収録物名
Biomaterials
巻(号)
32(18)
ページ
4306-4316
抄録
Previously, we developed a multifunctional envelope-type nano device (MEND) for efficient delivery of nucleic acids. For tumor delivery of a MEND, PEGylation is a useful method, which confers a longer systemic circulation and tumor accumulation via the enhanced permeability and retention (EPR) effect. However, PEGylation inhibits cellular uptake and subsequent endosomal escape. To overcome this, we developed a PEG-peptide-DOPE (PPD) that is cleaved in a matrix metalloproteinase (MMP)-rich environment. In this study, we report on the systemic delivery of siRNA to tumors by employing a MEND that is modified with PPD (PPD-MEND). An in vitro study revealed that PPD modification accelerated both cellular uptake and endosomal escape, compared to a conventional PEG modified MEND. To balance both systemic stability and efficient activity, PPD-MEND was further co-modified with PEG-DSPE. As a result, the systemic administration of the optimized PPD-MEND resulted in an approximately 70% silencing activity in tumors, compared to non-treatment. Finally, a safety evaluation showed that the PPD-MEND showed no hepatotoxicity and innate immune stimulation. Furthermore, in a DNA microarray analysis in liver and spleen tissue, less gene alternation was found for the PPD-MEND compared to that for the PEG-unmodified MEND due to less accumulation in liver and spleen.
資源タイプ
学術雑誌論文
出版タイプ
Accepted Manuscript
PISSN
0142-9612
関連情報
PMID
21429576
関連情報 (isVersionOf)
出版社版DOI
https://doi.org/10.1016/j.biomaterials.2011.02.045