项目名称: 光控“四唑-烯”点击化学法原位制备生物可降解水凝胶和微凝胶用于蛋白质药物的控制释放
项目编号: No.51273137
项目类型: 面上项目
立项/批准年度: 2013
项目学科: 一般工业技术
项目作者: 邓超
作者单位: 苏州大学
项目金额: 80万元
中文摘要: 本项目探索光控"四唑-烯"点击化学法原位制备生物可降解荧光水凝胶和微凝胶用于蛋白质药物控制释放。该水凝胶由水溶性可降解聚合物(如透明质酸、胶原蛋白等)的甲基丙烯酸酯衍生物和聚环氧乙烷的四唑衍生物在低光强照射下交联制备。微凝胶由反相乳液法将聚合物水溶液乳化后光照交联方便制备。该方法有机结合了光聚合和常规"点击化学"的优点:1)具有常规"点击化学"的快速高效、专一和反应条件温和的优点,但无需铜盐等毒性催化剂;2)具有光聚合的时空可控的优点,但无需光引发剂;3)反应专一性的特点使负载的蛋白质不参与交联,可很好保持生物活性;4)制备的水凝胶发强荧光,可用于观察凝胶载体在体内的变化。本项目将具体研究用光控"四唑-烯" 点击化学法制备具有不同性能结构的生物可降解荧光水凝胶和微凝胶,并将其用于蛋白质抗肿瘤药物IFNα2b、IL-2和IL-12的长期局部控制释放,以期实现高效低毒的肿瘤蛋白质治疗。
中文关键词: 光控“四唑-烯”点击化学;原位水凝胶;纳米凝胶;蛋白质释放;肿瘤治疗
英文摘要: In this project, novel in situ forming fluorescent biodegradable hydrogels and microgels are designed and prepared via "Tetrazole-alkene" photo-click reaction between methacrylate-functionalized water-soluble biodegradable polymer (like hyaluronic acid, collagen), and tetrazole-functionalized star poly(ethylene oxide) (PEO). Microgels are prepared by inverse emulsion of aqueous droplets of water-soluble biodegradable polymer in continuous oil phase with an aid of oil-soluble surfactants and crosslinking via "Tetrazole-alkene" reaction. This "Tetrazole-alkene" strategy has elegantly combined advantages of photo-crosslinking and conventional click chemistry: (1) crosslinking reaction like conventional click chemistry is efficient, fast and highly specific under physiological conditions, but without copper catalyst; (2) crosslinking reaction like photo-polymerization allows excellent spatiotemporal control, but without use of photoinitiator; (3) the high specificity of "Tetrazole-alkene" click reaction avoids conjugation and thereby deactivation of bioactive proteins; (4) the fluorescent nature of hydrogels and microgels facilitates monitoring of crosslinking reaction as well as hydrogel integrity in vivo. In this project, a series of in situ macrogels and microgels with different structure and physical properties
英文关键词: “tetrazole-alkene” photo-click chemistry;in situ hydrogels;nanogels;protein release;cancer therapy