Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection

Kai Li, Hikari Sato, Chan Woo Kim, Yuta Nakamura, Guo Xi Zhao, Daiki Funamoto, Takanobu Nobori, Akihiro Kishimura, Takeshi Mori, Yoshiki Katayama

研究成果: ジャーナルへの寄稿記事

1 引用 (Scopus)

抄録

We synthesized polymeric gene carriers consisting of poly-L-lysine (PLL) main chain modified both with substrate peptide for protein kinase C (PKC) and alkanethiol (pentadecanethiol). Due to the grafted substrate peptide, the polyplex prepared from these carriers is expected to show gene expression triggered by the phosphorylation of the peptide by intracellular PKC. The modified alkanethiol on the main chain stabilized the polyplex both via disulfide crosslinking and hydrophobic interaction. The polyplex found to show gene expression in vitro when the alkanethiol content in the main chain was enough low (4-mol%-modification of PLLs ε-amine group) to minimize cytotoxic effect. Even though the content of alkanethiol is low, the polyplex had significant stability in a model serum solution and showed longer blood circulation in vivo. The polyplex clearly accumulated in tumor after intravenous injection.

元の言語英語
ページ(範囲)657-668
ページ数12
ジャーナルJournal of Biomaterials Science, Polymer Edition
26
発行部数11
DOI
出版物ステータス出版済み - 7 24 2015

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Intravenous Injections
Protein Kinases
Peptides
Tumors
DNA
Genes
Proteins
Gene expression
Protein Kinase C
Gene Expression
Neoplasms
Phosphorylation
Blood Circulation
Hemodynamics
Substrates
Phase locked loops
Hydrophobic and Hydrophilic Interactions
Disulfides
Crosslinking
Lysine

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Bioengineering
  • Biomaterials
  • Biomedical Engineering

これを引用

Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection. / Li, Kai; Sato, Hikari; Kim, Chan Woo; Nakamura, Yuta; Zhao, Guo Xi; Funamoto, Daiki; Nobori, Takanobu; Kishimura, Akihiro; Mori, Takeshi; Katayama, Yoshiki.

:: Journal of Biomaterials Science, Polymer Edition, 巻 26, 番号 11, 24.07.2015, p. 657-668.

研究成果: ジャーナルへの寄稿記事

Li, Kai ; Sato, Hikari ; Kim, Chan Woo ; Nakamura, Yuta ; Zhao, Guo Xi ; Funamoto, Daiki ; Nobori, Takanobu ; Kishimura, Akihiro ; Mori, Takeshi ; Katayama, Yoshiki. / Tumor accumulation of protein kinase-responsive gene carrier/DNA polyplex stabilized by alkanethiol for intravenous injection. :: Journal of Biomaterials Science, Polymer Edition. 2015 ; 巻 26, 番号 11. pp. 657-668.
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abstract = "We synthesized polymeric gene carriers consisting of poly-L-lysine (PLL) main chain modified both with substrate peptide for protein kinase C (PKC) and alkanethiol (pentadecanethiol). Due to the grafted substrate peptide, the polyplex prepared from these carriers is expected to show gene expression triggered by the phosphorylation of the peptide by intracellular PKC. The modified alkanethiol on the main chain stabilized the polyplex both via disulfide crosslinking and hydrophobic interaction. The polyplex found to show gene expression in vitro when the alkanethiol content in the main chain was enough low (4-mol{\%}-modification of PLLs ε-amine group) to minimize cytotoxic effect. Even though the content of alkanethiol is low, the polyplex had significant stability in a model serum solution and showed longer blood circulation in vivo. The polyplex clearly accumulated in tumor after intravenous injection.",
author = "Kai Li and Hikari Sato and Kim, {Chan Woo} and Yuta Nakamura and Zhao, {Guo Xi} and Daiki Funamoto and Takanobu Nobori and Akihiro Kishimura and Takeshi Mori and Yoshiki Katayama",
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AU - Li, Kai

AU - Sato, Hikari

AU - Kim, Chan Woo

AU - Nakamura, Yuta

AU - Zhao, Guo Xi

AU - Funamoto, Daiki

AU - Nobori, Takanobu

AU - Kishimura, Akihiro

AU - Mori, Takeshi

AU - Katayama, Yoshiki

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N2 - We synthesized polymeric gene carriers consisting of poly-L-lysine (PLL) main chain modified both with substrate peptide for protein kinase C (PKC) and alkanethiol (pentadecanethiol). Due to the grafted substrate peptide, the polyplex prepared from these carriers is expected to show gene expression triggered by the phosphorylation of the peptide by intracellular PKC. The modified alkanethiol on the main chain stabilized the polyplex both via disulfide crosslinking and hydrophobic interaction. The polyplex found to show gene expression in vitro when the alkanethiol content in the main chain was enough low (4-mol%-modification of PLLs ε-amine group) to minimize cytotoxic effect. Even though the content of alkanethiol is low, the polyplex had significant stability in a model serum solution and showed longer blood circulation in vivo. The polyplex clearly accumulated in tumor after intravenous injection.

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