Tappertzhofen Kristof, Beck Simone, Montermann Evelyn, Huesmann David, Barz Matthias, Koynov Kaloian, Bros Matthias, Zentel Rudolf
Institute of Organic Chemistry, Johannes Gutenberg-University, Duesbergweg 10-14, 55128, Mainz, Germany.
MAINZ Graduate School of Excellence (Materials Science in Mainz), Johannes Gutenberg-University, Staudingerweg 9, 55128, Mainz, Germany.
Macromol Biosci. 2016 Jan;16(1):106-20. doi: 10.1002/mabi.201500212. Epub 2015 Jul 29.
Polylysine-b-p[HPMA] block copolymers containing a redox-responsive disulfide bond between both blocks are synthesized by RAFT polymerization of pentafluorphenyl-methacrylate with a macro-CTA from Nϵ-benzyloxycarbonyl (Cbz) protected polylysine (synthesized by NCA polymerization). This polylysine-b-p[PFMA] precursor block copolymer is converted to polylysine(Cbz)-b-p[HPMA] by postpolymerization modification with 2-hydroxypropylamine. After removal of the Cbz protecting group, cationic polylysine-b-p[HPMA] copolymers with a biosplittable disulfide moiety became available, which can be used as polymeric transfection vectors. These disulfide linked polylysine-S-S-b-p[HPMA] block copolymers show low cytotoxicity and increased transfection efficiencies (HEK-293T cells) compared to analogous blockcopolymers without disulfide group making them interesting for the transfection of sensitive immune cells.
通过五氟苯基甲基丙烯酸酯与来自Nϵ-苄氧羰基（Cbz）保护的聚赖氨酸（通过NCA聚合合成）的大分子CTA进行RAFT聚合，合成了在两个嵌段之间含有氧化还原响应性二硫键的聚赖氨酸-b-p[HPMA]嵌段共聚物。该聚赖氨酸-b-p[PFMA]前体嵌段共聚物通过用2-羟丙胺进行后聚合改性转化为聚赖氨酸（Cbz）-b-p[HPMA]。除去Cbz保护基团后，得到具有生物可裂解二硫部分的阳离子聚赖氨酸-b-p[HPMA]共聚物，其可用作聚合物转染载体。与没有二硫基团的类似嵌段共聚物相比，这些二硫键连接的聚赖氨酸-S-S-b-p[HPMA]嵌段共聚物显示出低细胞毒性和提高的转染效率（HEK-293T细胞），这使得它们对于敏感免疫细胞的转染很有意义。
