Histidinylated poly-L-lysine-based vectors for cancer-specific gene expression via enhancing the endosomal escape

Guo Xi Zhao, Hiroyuki Tanaka, Chan Woo Kim, Kai Li, Daiki Funamoto, Takanobu Nobori, Yuta Nakamura, Takuro Niidome, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama

研究成果: Contribution to journalArticle査読

8 被引用数 (Scopus)

抄録

In this work, we synthesized a series of poly-L-lysine (PLL)-based polymers for gene delivery, by modifying the PLL with both cationic peptide and histidine. The peptide moieties serve as cationic centers for polyplex formation, and also as substrates for protein kinase Cα (PKCα), which is specifically activated in many types of cancer cells, to achieve cancer-specific gene expression. The histidine groups serve as buffering moieties to increase the ability of the plasmid DNA (pDNA)-polymer complex (polyplex) to escape the endosome and thus to promote expression of the pDNA in the transfected cells. The facile synthesis of the polymers proceeded by modifying the PLL with side-group-protected peptide and protected histidine, followed by deprotection of the functional groups. The synthesized polymers showed significant buffering capacity over the neutral to acidic pH range and showed less cytotoxicity in vitro compared with histidine-unmodified polymers. The polyplexes successfully showed PKCα-responsive gene expression immediately after their introduction into cancer cells and the gene expression continued for at least 24 h. These PLL-based carriers thus show promise for cancer-targeted gene therapy.

本文言語英語
ページ(範囲)519-534
ページ数16
ジャーナルJournal of Biomaterials Science, Polymer Edition
25
5
DOI
出版ステータス出版済み - 3 24 2014

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

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