Molecular Architecture Governs Cytotoxicity and Gene Transfection Efficacy of Polyethylenimine Based Nanoplexes in Mammalian Cell Lines

التفاصيل البيبلوغرافية
العنوان: Molecular Architecture Governs Cytotoxicity and Gene Transfection Efficacy of Polyethylenimine Based Nanoplexes in Mammalian Cell Lines
المؤلفون: David Tai Leong, Lay Poh Tan, Nandita Menon, Chor Yong Tay
المصدر: Journal of Inorganic and Organometallic Polymers and Materials. 25:301-311
بيانات النشر: Springer Science and Business Media LLC, 2014.
سنة النشر: 2014
مصطلحات موضوعية: Polyethylenimine, Polymers and Plastics, biology, Chemistry, technology, industry, and agriculture, macromolecular substances, Transfection, Gene delivery, biology.organism_classification, Molecular biology, In vitro, HeLa, chemistry.chemical_compound, In vivo, Cell culture, Materials Chemistry, Biophysics, Cytotoxicity
الوصف: Polyethylenimine (pEI) is a potent cationic transfection agent that is commonly used in conjunction with other inorganic and organometallics formulations. However, the toxicity that is intrinsic to pEI constitutes a major obstacle for both in vitro and in vivo applications. In this study, the roles of pEI molecular architectures and effects of nitrogen/phosphate (N/P) molar ratio on the cytotoxic potential and in vitro transfection performance were elucidated utilizing linear (L-pEI) and branched (B-pEI) 25 kDa pEI. Both L-pEI and B-pEI were able to self-assemble with the plasmid DNA to form positively charged nanoplexes having an average hydrodynamic diameter of 100–150 nm. In vitro cytotoxicity and transfection performance were assessed with three model mammalian cell lines namely, L929, COS-7 and HeLa cells. Transfection profiles over a wide range of N/P ratio exemplify a similar trend across three different cell lines, with B-pEI nanoplexes consistently showing maximum transgene expression of enhanced green fluorescent protein at an earlier N/P ratio compared to L-pEI nanoplexes. However, high transfection activity was maintained over a wider N/P ratio for L-pEI nanoplexes. While the absolute size of the nanoplexes exhibited no discernible effect on the transfection performance, cytotoxicity of free un-bound B-pEI was identified as the dictating factor responsible for the observed global cellular response. Collectively, our findings provided critical insights into the role of pEI molecular architecture in cellular transfection and are expected to lay the foundation for the rational design and development of advanced pEI-based inorganic and organometallic gene delivery systems.
تدمد: 1574-1451
1574-1443
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_________::0888e8af13efb6abb5cbc08a03aedc7e
https://doi.org/10.1007/s10904-014-0135-8
حقوق: CLOSED
رقم الأكسشن: edsair.doi...........0888e8af13efb6abb5cbc08a03aedc7e
قاعدة البيانات: OpenAIRE