Development of Cancer Imaging System by Using Cell Signal-Responsive Molecular System

利用细胞信号响应分子系统开发癌症成像系统

• 批准号: 20300168
• 负责人: KATAYAMA Yoshiki
• 金额: $ 12.73万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20300168/
• 关键词: 遺伝子送達; プロテインキナーゼ; 細胞内情報伝達; DDS; in vivoイメージング; 細胞内シグナル; ペプチド; 遺伝子キャリヤー; 遺伝子治療; バイオイメージング; 診断

In this research, molecular systems which can visualize an activity of target protein kinase have been developed. First of all, we successfully developed protein kinase Cα-responsive system. The system visualized various tumors in mice. Second, fluorescence probe of PKCα was also prepared. In this system, fluorescence labeled polyanion was used instead of reporter gene. Another fluorescent probe of PKCα was also designed by using an electrostatic complex between quencher-labeled condroitin sulfate and a PAMAM dendrimer labeled with fluorophre and substrate peptide. In addition, signal responsibility of the reporter gene regulation system improved dramatically by changing the polymer backbone from neutral polyacrylamide to polyethylene imine. Various novel substrate specific to various protein kinases relating to cancer functions have also be developed successfully.

在这项研究中，已经开发了可以可视化目标蛋白激酶活性的分子系统。首先，我们成功地开发了蛋白激酶Cα反应系统。该系统显示了小鼠体内的各种肿瘤。其次，还制备了PKCα的荧光探针。在该体系中，用荧光标记的聚阴离子代替了报告基因。利用猝灭剂标记的硫酸软骨素与荧光标记的PAMAM树状大分子和底物多肽形成的静电络合物，设计了另一种PKCα的荧光探针。此外，报告基因调控系统的信号响应通过将聚合物主链从中性聚丙烯酰胺改变为聚乙烯亚胺而显著提高。与癌症功能相关的各种蛋白激酶的各种新底物也被成功地开发出来。

项目成果

Intracellular Signal-responsive Transgene Regulation Delivery System for Cell-specific Gene Therapy and Imaging.

用于细胞特异性基因治疗和成像的细胞内信号响应转基因调控传递系统。

• 发表时间: 2010
• 作者: Kamakura S;Anada T;Suzuki O.;山本隆夫,永井健一,菅幹生;Y.Katayama;片山佳樹
• 通讯作者: 片山佳樹

Protein Kinase Calpha-Responsive Gene regulation System for cancer gene therapy and Imaging

用于癌症基因治疗和成像的蛋白激酶 Cα 响应基因调控系统

• 发表时间: 2009
• 作者: Y.Katayama;R.Toita;T.Tomiyama;J-H.Kang;T.Mori;T.Niidome
• 通讯作者: T.Niidome

PKC alpha-Responsive Gene Regulatior for Cancer Cell-Specific Imaging and Therapy.

用于癌细胞特异性成像和治疗的 PKC α 响应基因调节。

• 发表时间: 2009
• 作者: 片山佳樹;et al
• 通讯作者: et al

細胞対話型分子システムを用いる革新的遺伝子送達概念の創製

使用细胞交互分子系统创建创新的基因传递概念

• 发表时间: 2008
• 作者: Y.Katayama;J-H.Kang;R.Toita;T.Tomiyama;D.Asai;T.Mori;T.Niidome;片山佳樹;片山佳樹
• 通讯作者: 片山佳樹

Characterization of gene expression regulation using D-RECS polymer by enzymatic reaction for an effective design of enzyme-responsive gene regulator.

使用 D-RECS 聚合物通过酶反应表征基因表达调控，以有效设计酶响应基因调控因子。

• DOI: 10.1016/j.jconrel.2010.01.013
• 发表时间: 2010
• 期刊: Journal of controlled release : official journal of the Controlled Release Society
• 作者: Yuko T. Sato;K. Kawamura;T. Niidome;Y. Katayama
• 通讯作者: Y. Katayama