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

设计了由3-硅-3,3-二甲基五亚甲基和N，N'-二乙基乙二胺交替组成的新型刺激敏感聚硅胺。通过改变环境pH值，聚硅胺呈现棒状-球状转变，即质子化聚硅胺在低pH值下呈现亲水性和刚性延伸构象，而非质子化聚硅胺在高pH值下呈现柔性疏水性材料。化学交联聚硅胺凝胶在pH值变化下呈现体积相变。当干凝胶在酸性条件下浸泡时，聚硅胺凝胶膨胀。与此同时，凝胶的网络变得僵硬。这与其他传统的水凝胶形成了鲜明的对比。传统的凝胶在膨胀时会变软。以端官能团聚硅胺为原料，制备了聚硅胺嵌段共聚物。所得嵌段共聚物与质粒DNA （pDNA）自发结合，形成PAMA/pDNA多离子复合物（PIC）核和PEG外壳的多聚胶束。在生理条件下，在N/P（共聚物中氨基数/pDNA中磷酸基数）比大于3的条件下制备的peg -聚硅胺/pDNA多聚胶束能够凝聚pDNA，因此采用相对较小的尺寸（<150 nm）和几乎中性的表面电荷（ζ ~ +5 mV）。胶束经历了pH诱导的尺寸变化(pH=7.4, 132.6 nm至。pH=4.0, 181.8 nm)，可能是由于聚硅胺链的构象变化（球棒转变）响应pH，导致聚硅胺内壳在较低的pH下膨胀。通过asialalglycoprotein （ASGP）受体介导的内吞作用，胶束表现出特定的细胞摄取进入HuH-7细胞（肝细胞），并且由于在胶束的PEG链末端安装了乳糖，从而实现了更有效的报告基因转染能力。因此，由配体-聚乙二醇/聚硅胺嵌段共聚物组成的复合胶束将是一种具有靶向性和内体破坏性的非病毒基因载体。少

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