基于门舒特金反应的酶触发自降解高分子载体及其在基因输送中的应用

发布时间：2018-02-04 20:29

本文关键词： 基因输送阳离子聚合物触发自降解门舒特金反应酯酶响应　出处：《高分子学报》2017年06期 　论文类型：期刊论文

【摘要】：用邻位苄基溴与双胺进行门舒特金反应,合成了2种线性的季铵盐阳离子聚合物.其中,含有酚基酯键的阳离子聚合物,一旦进入细胞后,可以在细胞内的酯酶催化下快速水解,使得聚合物自降解断裂为不带电的非季铵盐小分子,从而快速释放DNA,最终达到提高转染效率的目的.通过对复合物纳米颗粒的粒径和电势测定,证明了这2种阳离子聚合物都能够有效地结合DNA形成表面带正电的复合物纳米颗粒.凝胶阻滞电泳实验表明,所合成的阳离子聚合物都能稳定地包裹DNA.而在酯酶条件下,含有酚基酯键的阳离子聚合物可以发生降解,使得纳米复合物释放出DNA.同时,含有酚基酯键的阳离子聚合物由于其独特的可降解性,相比于PEI,降低了细胞毒性.在体外细胞转染实验中,2种阳离子聚合物都有较好的转染效果.其中酯酶响应的载体在高N/P下依然表现出较高的转染效率,说明该阳离子载体能够在细胞内有效降解并释放出DNA.
[Abstract]:Two linear quaternary ammonium salts cationic polymers were synthesized by the gate Shutkin reaction of o-benzyl bromide with diamine. It can be hydrolyzed rapidly under the catalysis of intracellular esterase, which makes the polymer self-degrade and break into non-charged non-quaternary ammonium salt small molecules, thus releasing DNA quickly. Finally, the transfection efficiency was improved. The particle size and potential of the nanoparticles were measured. It was proved that the two cationic polymers could effectively combine with DNA to form composite nanoparticles with positive charge on the surface. The synthesized cationic polymers can encapsulate DNA stably. However, under esterase conditions, the cationic polymers containing phenolic ester bonds can be degraded, resulting in the release of DNA. at the same time. The cationic polymer containing phenolic ester bond is less cytotoxic than PEI because of its unique biodegradability. The two cationic polymers had good transfection effect, and the esterase response vector still showed high transfection efficiency at high N / P level. The results showed that the cationic carrier could effectively degrade and release DNA in cells.
【作者单位】：生物质化工教育部重点实验室浙江大学化学工程与生物工程学院;
【基金】：国家重点基础研究发展计划(973计划,项目号2014CB931900) 国家自然科学基金(基金号51403185)资助项目
【分类号】：O631;R450
【正文快照】： **通讯联系人,E-mail:shenyq@zju.edu.cn基因治疗指的是将外源正常基因导入靶细胞,以纠正或补偿因基因缺陷和异常引起的疾病,达到治疗目的.基因治疗不仅要求治疗性基因在目标靶位高效表达[1],同时也要求所使用的载体必须低毒安全[2].虽然病毒基因载体有很高的转染效率,但是其

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