Design for Novel Stimuli-Sensitive Hydrogel, Polysilamine, and its Materials Design

新型刺激敏感水凝胶聚硅胺的设计及其材料设计

• 批准号: 14350502
• 负责人: NAGASAKI Yukio
• 金额: $ 6.21万
• 依托单位: UNIVERSITY OF TSUKUBA (2004-2005)Tokyo University of Science (2002-2003)
• 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 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-14350502/
• 关键词: poly(silamine); stimuli-sensitive hydrogel; rod-globule transition; Gene delivery; gene vector; DDS; intercellular trafficing; ロッド-グロビュール転移; PEG; ポリサイラミンブロック共重合体; ポリイオンコンプレックスミセル; 遺伝子キャリア; 環境応答性; ゴム弾性転移; 遺伝子治療; バイオナノ粒子; pH応答性ハイドロゲル; 力学特性

Novel stimuli-sensitive poly(silamine), which consists of alternating 3-sila-3,3-dimethylpentamethylene and N,N'-diethyl-ethylenediamine, was designed. The poly(silamine) showed rod-globule transition by chaiging environmental pH change, viz., protonated poly(silamine) was hydrophilic and stiff extended conformation under low pH, while non-protonated poly(silamine) was flexsible hydrophobic material under high pH. Chemically crosslinked poly(silamine) gel showed an volume phase transition by pH change. When xerogel was soaked in acidic condition, the poly(silamine) gel swelled. At the same time, the network of the gel become stiff. This is striking contrast to other conventional hydrogel. Conventional gel becomes soft when it swells.Using end functional poly(silamine), PEG-poly(silamine) block copolymer was prepared. The obtained block copolymer spontaneously associated with plasmid DNA (pDNA) to form polyplex micelles with a PAMA/pDNA polyion complex (PIC) core, and a PEG outer shell, … More as confirmed by ^1H NMR spectroscopy. Under physiological conditions, the PEG-poly(silamine)/pDNA polyplex micelles prepared at an N/P (number of amino groups in the copolymer/number of phosphate groups in pDNA) ratio above 3 were found to be able to condense pDNA, thus adopting a relatively small size (<150 nm) and an almost neutral surface charge (ζ〜+5 mV). The micelle underwent a pH-induced size variation (pH=7.4, 132.6 nm to. pH=4.0, 181.8 nm) presumably due to the conformational changes (globule-rod transition) of the poly(silamine) chain in response to pH, leading to swelling of the poly(silamine) inner shell at lowered pH. Furthermore, the micelles exhibited a specific cellular uptake into HuH-7 cells (hepatocytes) through asialoglycoprotein (ASGP) receptor-mediated endocytosis and achieved a far more efficient transfection ability of a reporter gene because of the installation of lactose at the end of PEG chain of the micelle. Therefore, the polyplex micelle composed of Ligand-PEG/poly(silamine) block copolymer would be a promising approach to a targetable and endosome disruptive nonviral gene vector. Less

设计了由3-硅氧烷-3，3-二甲基五亚甲基和N，N‘-二乙二胺交替组成的新型刺激性聚硅胺。聚硅胺受环境pH变化的影响呈棒状-球状转变，即质子化聚硅胺在低pH下呈亲水性和刚性伸展构象，而非质子化聚硅胺在高pH下为柔性疏水材料。化学交联聚(硅胺)凝胶的pH变化使凝胶发生体积相变。当干凝胶在酸性条件下浸泡时，聚硅胺凝胶发生溶胀。与此同时，凝胶的网络变得僵硬。这与其他传统水凝胶形成了鲜明的对比。利用端基官能化聚硅胺制备了聚乙二醇聚硅胺嵌段共聚物。得到的嵌段共聚物与pDNA自发结合形成以PAMA/pDNA多离子络合物(PIC)为核心和聚乙二醇壳…为外壳的复合胶束更多的是由^1H核磁共振波谱证实的。在生理条件下，N/P(共聚物中的氨基数目/DNA中的磷酸基数)大于3的聚乙二醇聚硅胺/聚DNA复合胶束能够凝聚聚DNA，从而具有相对较小的尺寸(~lt；150 nm)和几乎中性的表面电荷(ζ~+5 mV)。胶束的大小随pH的变化而变化(pH=7.4,132.6 nm)。PH=4.0,181.8 nm)可能是由于聚硅胺链的构象变化(球状-棒状转变)对pH的响应，导致聚硅胺内壳在较低的pH下膨胀。此外，该胶束通过去唾液酸糖蛋白(ASGP)受体介导的内吞作用对HH-7细胞(肝细胞)具有特异性的细胞摄取作用，并且由于乳糖安装在胶束的聚乙二醇链的末端，实现了更有效的报告基因的转染能力。因此，由配体-聚乙二醇聚硅胺嵌段共聚物组成的复合胶束有望成为靶向性和内吞体扰断型非病毒基因载体。较少

项目成果

Intracellular inducible alkylation system that exhibits antisense effects with greater potency and selectivity than natural oligonucleotid

细胞内诱导型烷基化系统，表现出比天然寡核苷酸更高的效力和选择性的反义效应

• 发表时间: 2006
• 期刊: Angewandte Chemie International Edition (in press)
• 作者: 長崎幸夫;長崎幸夫
• 通讯作者: 長崎幸夫

Synthesis of Heterotelechelic Poly(ethylene glycol) Derivatives Having alpha-Benzaldehyde and omega-Pyridyl Disulfide Groups by Ring Opening Polymerization of Ethylene Oxide Using 4-(diethoxymethyl)benzyl Alkoxide as Novel Initiator

以4-(二乙氧基甲基)苯甲醇盐为新型引发剂环氧乙烷开环聚合合成具有α-苯甲醛和Ω-吡啶基二硫基团的杂遥爪聚乙二醇衍生物

• 发表时间: 2004
• 期刊: Bioconjugate Chemistry 15
• 作者: Motoi Oishi;Yukio Nagasaki;Keiji Itaka;Nobuhiro Nishiyama;Kazunori Kataoka;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫
• 通讯作者: 長崎幸夫

Preparation of Functionally PEGylated Gold Nanoparticles with Narrow Distribution through Autoreduction of Auric Cation by alpha-Biotinyl-PEG-block-[poly(2-(N,N-dimethylamino)ethyl methacrylate)]

α-生物素-PEG-嵌段-[聚(2-(N,N-二甲氨基)乙基甲基丙烯酸酯)]自还原金阳离子制备窄分布功能性聚乙二醇化金纳米粒子

• 发表时间: 2004
• 期刊: Langmuir 20
• 作者: 目谷 浩通;目谷 浩通;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫;長崎幸夫
• 通讯作者: 長崎幸夫

長崎幸夫: "ナノマテリアル最前線 現実になった究極のものづくり -化学フロンティア,平尾 一之編"化学同人. 10 (2002)

长崎由纪夫：“纳米材料的前沿：已成为现实的终极制造 - 化学前沿，平尾和幸编辑”化学同人 10 (2002)。

長崎幸夫, Mari Tabuchi, Masanori Ueda, Noritada Kaji, Yuichi Yamasaki, Yukio Nagasaki, Kenichi Yoshikawa, Kazunori Kataoka, Yoshinobu Baba: "Nanospheres for DNA separation chips"Nature Biotech.. Vol.22, March 3. 337-340 (2004)

Yukio Nagasaki、Mari Tabuchi、Masanori Ueda、Noritada Kaji、Yuichi Yamasaki、Yukio Nagasaki、Kenichi Yoshikawa、Kazunori Kataoka、Yoshinobu Baba：“DNA分离芯片的纳米球”Nature Biotech.. Vol.22，3月3.337-340（2004年） ）