Effective transgene expression without toxicity by intraperitoneal administration of PEG-detachable polyplex micelles in mice with peritoneal dissemination

Michiaki Kumagai, Shinya Shimoda, Rie Wakabayashi, Yumi Kunisawa, Takehiko Ishii, Kensuke Osada, Keiji Itaka, Nobuhiro Nishiyama, Kazunori Kataoka, Kenji Nakano

研究成果: Contribution to journalArticle査読

19 被引用数 (Scopus)

抄録

Block copolymer of poly(ethylene glycol)-block-poly{N-[N-(2-aminoethyl)-2- aminoethyl]aspartamide} (PEG-P[Asp(DET)]) has been originally introduced as a promising gene carrier by forming a nanomicelle with plasmid DNA. In this study, the polyplex micelle of PEG-SS-P[Asp(DET)], which disulfide linkage (SS) between PEG and cationic polymer can detach the surrounding PEG chains upon intracellular reduction, was firstly evaluated with respect to in vivo transduction efficiency and toxicity in comparison to that of PEG-P[Asp(DET)] in peritoneally disseminated cancer model. Intraperitoneal (i.p.) administration of PEG-SS-P[Asp(DET)] polyplex micelles showed a higher (P < 0.05) transgene expression compared with PEG-P[Asp(DET)] in tumors. In contrast, the delivered distribution of the micelles was not different between the two polyplex micelles. PEG-SS-P[Asp(DET)] micelle encapsulating human tumor necrosis factor α (hTNF-α) gene exhibits a higher antitumor efficacy against disseminated cancer compared with PEG-P[Asp(DET)] or saline control. No hepatic and renal toxicities were observed by the administration of polyplex micelles. In conclusion, PEG-detachable polyplex micelles may represent an advantage in gene transduction in vivo over PEG-undetachable polyplex micelles after i.p. administration for peritoneal dissemination of cancer.

本文言語英語
ページ(範囲)542-551
ページ数10
ジャーナルJournal of Controlled Release
160
3
DOI
出版ステータス出版済み - 6 28 2012

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science

フィンガープリント 「Effective transgene expression without toxicity by intraperitoneal administration of PEG-detachable polyplex micelles in mice with peritoneal dissemination」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

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