Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, Sichuan University, Chengdu 610064, P. R. China.
J Mater Chem B. 2020 Mar 18;8(11):2275-2285. doi: 10.1039/c9tb02528f.
Cationic polymers have shown great potential in the delivery of nucleic acids and proteins. In this study, a series of pyrimidine-based cationic polymers were synthesized via the Michael addition reaction from pyrimidine-based linkages and low molecular weight polyethyleneimine (PEI). The structure-activity relationship (SAR) of these materials in DNA and protein delivery was investigated. These materials could condense both DNA and protein into nanoparticles with proper sizes and zeta-potentials. In vitro experiments indicated that such polymers were efficient in transporting DNA and proteins into cells. Furthermore, the bioactivity of the genes and proteins encapsulated in these polymers were maintained during the delivery processes. Among the polymers, U-PEI600 synthesized from a uracil-containing linker and PEI 600 Da mediated comparable gene expression to PEI 25 kDa. Moreover, the activities of β-galactosidase delivered by U-PEI600 were well maintained after entering the cells. Evaluation using an immune response assay showed that the U-PEI600/OVA polyplex could stimulate greater production of immune factors with low cytotoxicity. Our study provides a strategy for the construction of cationic polymeric gene and cytosolic protein vectors with high efficiency and low toxicity.
阳离子聚合物在核酸和蛋白质的递送上显示出巨大的潜力。在这项研究中，通过嘧啶键和低分子量聚乙烯亚胺（PEI）的迈克尔加成反应，合成了一系列基于嘧啶的阳离子聚合物。研究了这些材料在 DNA 和蛋白质递送上的结构-活性关系（SAR）。这些材料可以将 DNA 和蛋白质适当大小和zeta 电位的纳米颗粒。体外实验表明，这些聚合物能够有效地将 DNA 和蛋白质输送到细胞中。此外，封装在这些聚合物中的基因和蛋白质的生物活性在输送过程中得以保持。在这些聚合物中，由含尿嘧啶的连接子和 600 Da 的 PEI 合成的 U-PEI600 介导的基因表达与 25 kDa 的 PEI 相当。此外，进入细胞后，U-PEI600 递送的β-半乳糖苷酶活性得到很好的保持。免疫反应试验评估表明，U-PEI600/OVA 聚合物能够刺激产生具有低细胞毒性的免疫因子。我们的研究为构建高效低毒的阳离子聚合物基因和细胞质蛋白载体提供了一种策略。
