新型纳米纤维素基基因载体的构建、制备及性能研究

Cellulose nanofibers, isolated from biosources, such as wood, straw, and cotton, possess many intriguing properties including high purity, biodegradability, readily preparation and renewable nature. In particular, cellulose nanofibers also have good cell membrane-penetrating abilities similar to those of carbon nanotubes. The above properties make cellulose nanfibers attractive components of a broad range of advanced biomaterials. Based on our earlier research results of polysaccharide-based gene carriers, this proposal would provide a new idea to construct disulfide bonds-containing and functional biomolecule-taking cellulose nanofiber-based gene carriers by combining atom transfer radical polymerization (ATRP) or reversible addition-fragmentation chain transfer polymerization (RAFT) with postmodifcation. First, the disulfide bonds-containing initiation sites on cellulose nanofibers are constructed via activating some hydroxyl groups. Then, poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA) and polyethylene glycol (PEG) brushes were prepared on the nanofiber surfaces via ATRP or RAFT methods. Finally, some remaining hydroxyl groups of fiber surfaces are activated for coupling different functional biomolecules including phospholipid, cholic acid, folic acid and peptides. Such biomolecules could further introduce the desirable biophysical properties such as cell membrane-mimic, penetrating and targeting abilities, leading to new types of highly effective and low-toxic multifunctional cellulose nanofiber-based gene carriers.

棒状纳米天然多糖纤维素具有高纯度、可降解、生物相容及可再生等特性，特别是拥有类碳纳米管的细胞膜穿透能力，非常适于制备高性能生物材料的研发。本项目预在申请者原有的天然多糖基基因载体的研究基础上，力图以纳米纤维素颗粒为基点，结合ATRP法、RAFT法以及功能性生物分子后续修饰等手段，构建出含可剪切二硫键、可携带特定生物分子的新型纳米纤维素基基因载体。首先在纳米纤维素表面引入含有二硫键的ATRP或RAFT引发官能团；然后，通过ATRP法或RAFT法在纳米纤维素表面引入PDMAEMA和PEG 聚合刷；最后，激活纳米纤维素表面的部分剩余羟基引入生物小分子，包括磷脂、多肽、胆酸以及叶酸等分子。载体的 PEG 化可增加载体的屏蔽效应，磷脂功能化可引入类似脂质体或细胞膜结构以提高载体的生物特性，肽功能化可增加载体的特定生物功能，靶向化可提高载体的细胞靶向性。最终构建出多功能性新型纳米纤维素基基因载体。

棒状纳米天然多糖纤维素具有高纯度、可降解、生物相容及可再生等特性，非常适于制备高性能递送载体的研发。本项目以纳米纤维素颗粒为基点，结合ATRP法、RAFT法以及功能性生物分子后续修饰等手段，构建出含可剪切二硫键、具有特定功能的、以纳米纤维素为主的多糖基基因载体。首先在纳米纤维素表面引入含有二硫键的ATRP或RAFT引发官能团；然后，通过ATRP法或RAFT法在纳米纤维素表面引入阳离子或其他功能的聚合刷；此外，也通过超分子组装、有机无机杂化等方法，进一步拓展了基因载体的功能，最终构建出多功能性新型纳米纤维素基基因载体。