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.
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.