European Journal of Medicinal Chemistry ( IF 6.0 ) Pub Date : 2020-09-12 , DOI: 10.1016/j.ejmech.2020.112799 Ya-Ping Xiao , Ji Zhang , Yan-Hong Liu , Zheng Huang , Xiao-Qi Yu
Emulsions have shown great potential in the delivery of various types of cargoes such as nucleic acids and proteins. In this study, fluorinated polymer emulsions (PFx@PFD-n) were prepared using fluorinated polymers with different structures as surfactant in PFD emulsions under ultrasound. These polymer emulsions gave comparable DNA binding ability compared with corresponding polymers. Heparin competition experiment showed that polymer emulsions could compact DNA or protein to form more stable complexes. In vitro gene transfection results showed that the polymer emulsions could induce higher gene expression than corresponding polymers and polyethyleneimine (PEI), and the transfection efficiency was enhanced with the increase of PFD amount in polymer emulsions. Flow cytometry studies revealed that the emulsions could mediate more efficient cellular uptake with stronger serum tolerance. Moreover, the polymer emulsion could deliver considerable amount of OVA into Raw 264.7 cells at low mass ratio, showing its potential in immunotherapy. The activities of β-galactosidase delivered by the emulsions could also be well maintained after entering cells. This study provides a strategy to construct cationic gene and cytosolic protein vectors with high efficiency and low toxicity.
中文翻译:
氟化聚合物乳液系统:构建和应用在传递基因和蛋白质中
乳剂在递送各种类型的货物如核酸和蛋白质方面显示出巨大的潜力。在这项研究中,在超声作用下,使用具有不同结构的氟化聚合物作为表面活性剂在PFD乳液中制备了氟化聚合物乳液(PFx @ PFD-n)。与相应的聚合物相比,这些聚合物乳液具有可比的DNA结合能力。肝素竞争实验表明,聚合物乳液可以压实DNA或蛋白质,形成更稳定的复合物。体外基因转染结果表明,聚合物乳液比相应的聚合物和聚乙烯亚胺(PEI)诱导的基因表达更高,且随着乳液中PFD含量的增加,转染效率提高。流式细胞仪研究表明,乳剂可以介导更有效的细胞摄取,并具有更强的血清耐受性。此外,该聚合物乳液可以低质量比将大量的OVA输送到Raw 264.7细胞中,显示出其在免疫治疗中的潜力。进入细胞后,乳剂传递的β-半乳糖苷酶的活性也可以得到很好的维持。本研究为构建高效,低毒的阳离子基因和胞质蛋白载体提供了策略。