Zhang Yue, Zhang Jiamin, Xing Cheng, Zhang Mingming, Wang Lianyong, Zhao Hanying
Key Laboratory of Functional Polymer Materials, Ministry of Education, College of Chemistry, Nankai University, Tianjin 300071, China.
Collaborative Innovation Center of Chemical Science and Engineering, Nankai University, Tianjin 300071, China.
ACS Biomater Sci Eng. 2016 Dec 12;2(12):2266-2275. doi: 10.1021/acsbiomaterials.6b00490. Epub 2016 Oct 20.
There are many natural examples of smart structures that are able to change conformations and functionalities responding to the external stimuli. The responsiveness is directly related to their unique structures. In the design of new materials, it is crucial to endow these materials with the capabilities to change structures and functionalities under the external stimuli. In this research, virus-mimicking protein nanogels with temperature-induced reversible structures and redox responsiveness are synthesized by cross-linking a thermally responsive polymer poly(di(ethylene glycol) methyl ether methacrylate--2-(2-pyridyldisulfide) ethyl methacrylate) with reduced bovine serum albumin (BSA) molecules through thiol-disulfide exchange reaction. The lower critical solution temperature (LCST) and sizes of the nanogels can be controlled by controlling the reaction conditions. The nanogels are able to change their structures responding to the temperature change. Below the LCST, BSA molecules are embedded inside the nanogels and protected by the polymer chains. Above the LCST, polymer chains collapse forming the cores, and BSA moves to the shells to stabilize the nanogels. The disulfide-cross-linked nanogels are dissociated in the presence of glutathione. cytotoxicity assays and cell uptake assays demonstrate that the nanogels show low toxicity toward 3T3, 293T, and MCF-7 cells and can be internalized into the MCF-7 cells. The nanogels will find applications in protein delivery.
有许多能够响应外部刺激而改变构象和功能的智能结构的天然例子。这种响应性直接与其独特的结构相关。在新材料的设计中，赋予这些材料在外部刺激下改变结构和功能的能力至关重要。在本研究中，通过热响应性聚合物聚（二（乙二醇）甲基醚甲基丙烯酸酯 - 2-（2-吡啶二硫代）乙基甲基丙烯酸酯）与还原型牛血清白蛋白（BSA）分子通过硫醇 - 二硫键交换反应交联，合成了具有温度诱导可逆结构和氧化还原响应性的病毒模拟蛋白纳米凝胶。纳米凝胶的低临界溶液温度（LCST）和尺寸可以通过控制反应条件来控制。纳米凝胶能够响应温度变化而改变其结构。在LCST以下，BSA分子嵌入纳米凝胶内部并由聚合物链保护。在LCST以上，聚合物链坍塌形成核心，BSA移动到壳层以稳定纳米凝胶。二硫键交联的纳米凝胶在谷胱甘肽存在下会解离。细胞毒性测定和细胞摄取测定表明，纳米凝胶对3T3、293T和MCF-7细胞显示出低毒性，并且可以内化到MCF-7细胞中。这些纳米凝胶将在蛋白质递送中找到应用。
