Creation of intelligent polymeric micelle nanocapsuls for gene delivery

创建用于基因传递的智能聚合物胶束纳米胶囊

• 批准号: 14380391
• 负责人: KATAOKA Kazunori
• 金额: $ 10.62万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380391/
• 关键词: polymeric micelle; gene delivery; block copolymer; nanocapsul; DNA; Biocompartibility; polyethylene glycol

We investigated intelligent polymeric micelle nanocapsuls formed through the complexation of block copolymers and plasmid DNA, as non-viral gene vectors. The block copolymers are composed of a hydrophilic polyethylene glycol (PEG) and positively charged polyamino acids. To enhance the efficacy of gene expression, in particular in vivo system, novel strategy for the active targeting which can be realized through the introduction of pilot moiety on the surface of polymeric micelles should be established. For this purpose, we developed a synthetic scheme for block copolymers to employ multi-intelligent functions, i.e., prolonged circulation inside the blood vessel tubes, enhanced permeation from the blood vessel tubes toward tissues, selective transfection to the targeting tissues, enhanced cellular uptake due to the pilot moieties, smooth release of plasmid DNA inside the cells, etc.In addition, a wide adaptability for the length of plasmid DNA and also the environmental responsibility of the polymeric micelle nanocapsuls that should be essential to overcome the efficacy of viral gene delivery system were experimentally conformed. This system exhibits highly transfection potency not only in in vitro system but also in preliminary in vivo experiments. This multi-intelligent polymeric micelle nanocapsuls can be treated as an universal platform of non-viral gene delivery system.

我们研究了通过嵌段共聚物和质粒DNA的复合形成的智能聚合物胶束纳米胶囊，作为非病毒基因载体。嵌段共聚物由亲水性聚乙二醇（PEG）和带正电荷的聚氨基酸组成。为了提高基因表达的效率，特别是在体内系统中，主动靶向的新策略，可以通过在聚合物胶束表面引入先导基团来实现。为此，我们开发了一种嵌段共聚物的合成方案，以采用多智能功能，即，延长血管管内的循环、增强从血管管向组织的渗透、选择性转染至靶组织、由于先导部分而增强的细胞摄取、质粒DNA在细胞内的平稳释放等。此外，对质粒DNA长度的广泛适应性以及聚合物胶束纳米胶囊的环境响应性对于克服实验证实了病毒基因递送系统功效。该系统不仅在体外系统中而且在初步的体内实验中显示出高的转染效力。这种多智能聚合物胶束纳米囊可以作为非病毒基因传递系统的通用平台。

项目成果

Lactose-installed polyion complex micelles incorporating plasmid DNA as a targetable gene vector system : Their preparation and gene transfecting efficiency against cultured HepG2 cells

乳糖安装的聚离子复合胶束掺入质粒 DNA 作为靶向基因载体系统：其制备和对培养的 HepG2 细胞的基因转染效率

• 发表时间: 2004
• 期刊: J. Controlled Release 95(3)
• 作者: D.Wakebayashi;N.Nishiyama;Y.Yamasaki;K.Itaka;N.Kanayama;A.Harada;Y.Nagasaki;K.Kataoka
• 通讯作者: K.Kataoka

Effect of charged segment length on physicochemical properties of core-shell type polyion complex micelles from block ionomers

• DOI: 10.1021/ma025737i
• 发表时间: 2003-07-01
• 期刊: MACROMOLECULES
• 影响因子: 5.5
• 作者: Harada, A;Kataoka, K
• 通讯作者: Kataoka, K

K.Itaka, A.Harada, K.Nakamura, H.Kawaguchi, K.Kataoka: "Evaluation by fluorescence resonance energy transfer of the stability on nonviral gene delivery vectors under physiological conditions"Biomacromolecules. 3(4). 841-845 (2002)

K.Itaka、A.Harada、K.Nakamura、H.Kawaguchi、K.Kataoka：“通过荧光共振能量转移评估生理条件下非病毒基因递送载体的稳定性”生物大分子。

Versatile synthesis of end-functionalized thermosensitive poly(2-isopropyl-2-oxazolines)

• DOI: 10.1021/ma049677n
• 发表时间: 2004-09-07
• 期刊: MACROMOLECULES
• 影响因子: 5.5
• 作者: Park, JS;Akiyama, Y;Kataoka, K
• 通讯作者: Kataoka, K

Microcalorimetric study of the temperature-induced phase separation in aqueous solutions of poly(2-isopropyl-2-oxazolines)

• DOI: 10.1021/ma0358733
• 发表时间: 2004-04-06
• 期刊: MACROMOLECULES
• 影响因子: 5.5
• 作者: Diab, C;Akiyama, Y;Winnik, FM
• 通讯作者: Winnik, FM