Lipid-Modified PEI Derivative-Based Binary/Ternary Polyplex Formulations for the Delivery of pDNA and mRNA in Primary Cells.

IF 5.5 2区 化学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Amarnath Praphakar Rajendran, Daniel Nisakar Meenakshi Sundaram, Luis Carlos Morales, Cezary Kucharski, Mohammad Nasrullah, Burcak Bulut, Pavlo Michailo Tsisar, Aislinn D Maguire, Bradley J Kerr, Hasan Uludağ
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引用次数: 0

Abstract

A previous study has demonstrated the benefit of modification of polyethylenimine (PEI1.2k) by lipids through a p-hydroxyphenylacetic acid (PHPA) linker and polyanion (PA), which is now extended in this report to several primary cells. The formulated binary (lipopolymer/NAs) and ternary (lipopolymer/NAs/PA) complexes displayed no significant toxicity (MTT/hemolysis assay). The pDNA/mRNA complexes with PEI1.2k-PHPA-Lin9 and PEI1.2k-PHPA-Lau5-Ole5 lipopolymers showed gene expression levels higher than those of other lipopolymers. The transfection efficiencies of the ternary polyplexes of these lipopolymers possessed higher gene expression than those of the binary polyplexes. The serum-stable ternary polyplexes of PEI1.2k-PHPA-Lau5-Ole5 maintained high levels of mRNA expression in the lungs along with the spleen after intravenous injection. As in in vitro studies, transgene expression was relatively weak with binary complexes in muscle; however, a 10-fold higher efficiency was obtained with ternary complexes. Overall, our results provide improved gene formulations for the transfections of primary cells in vitro, as well as in in vivo animal models.

基于脂质修饰PEI衍生物的二/三元复合制剂用于原代细胞中pDNA和mRNA的递送。
先前的一项研究已经证明了脂质通过对羟基苯乙酸(PHPA)连接剂和聚阴离子(PA)修饰聚乙烯亚胺(PEI1.2k)的益处,现在在本报告中扩展到几个原代细胞。配制的二元(脂聚合物/NAs)和三元(脂聚合物/NAs/PA)复合物没有明显的毒性(MTT/溶血试验)。与PEI1.2k-PHPA-Lin9和PEI1.2k-PHPA-Lau5-Ole5脂聚合物的pDNA/mRNA复合物的基因表达水平高于其他脂聚合物。三聚体的转染效率高于二聚体的基因表达。经静脉注射后,血清稳定的三元复合物PEI1.2k-PHPA-Lau5-Ole5在肺和脾脏中保持高水平的mRNA表达。与体外研究一样,在肌肉中的二元复合物中,转基因表达相对较弱;然而,三元配合物的效率提高了10倍。总的来说,我们的结果为体外原代细胞转染以及体内动物模型提供了改进的基因配方。
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来源期刊
Biomacromolecules
Biomacromolecules 化学-高分子科学
CiteScore
10.60
自引率
4.80%
发文量
417
审稿时长
1.6 months
期刊介绍: Biomacromolecules is a leading forum for the dissemination of cutting-edge research at the interface of polymer science and biology. Submissions to Biomacromolecules should contain strong elements of innovation in terms of macromolecular design, synthesis and characterization, or in the application of polymer materials to biology and medicine. Topics covered by Biomacromolecules include, but are not exclusively limited to: sustainable polymers, polymers based on natural and renewable resources, degradable polymers, polymer conjugates, polymeric drugs, polymers in biocatalysis, biomacromolecular assembly, biomimetic polymers, polymer-biomineral hybrids, biomimetic-polymer processing, polymer recycling, bioactive polymer surfaces, original polymer design for biomedical applications such as immunotherapy, drug delivery, gene delivery, antimicrobial applications, diagnostic imaging and biosensing, polymers in tissue engineering and regenerative medicine, polymeric scaffolds and hydrogels for cell culture and delivery.
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