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Synergistic Effect of Low Molecular Weight Polyethylenimine and Polyethylene Glycol Components in Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency

“Petru Poni” Institute of Macromolecular Chemistry, Romanian Academy, Centre of Advanced Research in Bionanoconjugates and Biopolymers, Grigore Ghica Voda Alley, 41 A, 700487 Iasi, Romania
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Molecules 2019, 24(8), 1460; https://doi.org/10.3390/molecules24081460
Received: 19 March 2019 / Revised: 9 April 2019 / Accepted: 11 April 2019 / Published: 12 April 2019
(This article belongs to the Section Bioorganic Chemistry)
When studying polyethylenimine derivatives as nonviral vectors for gene delivery, among the important issues to be addressed are high toxicity, low transfection efficiency, and nucleic acid polyplex condensation. The molecular weight of polyethylenimine, PEGylation, biocompatibility and, also, supramolecular structure of potential carrier can all influence the nucleic acid condensation behavior, polyplex size, and transfection efficiency. The main challenge in building an efficient carrier is to find a correlation between the constituent components, as well as the synergy between them, to transport and to release, in a specific manner, different molecules of interest. In the present study, we investigated the synergy between components in dynamic combinatorial frameworks formed by connecting PEGylated squalene, poly-(ethyleneglycol)-bis(3-aminopropyl) and low molecular weight polyethylenimine components to 1,3,5-benzenetrialdehyde, via reversible imine bond, applying a dynamic combinatorial chemistry approach. We report comparative structural and morphological data, DNA binding affinity, toxicity and transfection efficiency concerning the ratio of polyethylenimine and presence or absence of poly-(ethyleneglycol)-bis(3-aminopropyl) in composition of dynamic combinatorial frameworks. In vitro biological assessments have revealed the fact that nonviral vectors containing poly-(ethyleneglycol)-bis(3-aminopropyl) and the lowest amount of polyethylenimine have significant transfection efficiency at N/P 50 ratio and display insignificant cytotoxicity on the HeLa cell line. View Full-Text
Keywords: drug delivery; dynamic combinatorial chemistry; supramolecular assembly; squalene; DNA condensation drug delivery; dynamic combinatorial chemistry; supramolecular assembly; squalene; DNA condensation
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MDPI and ACS Style

Craciun, B.F.; Gavril, G.; Peptanariu, D.; Ursu, L.E.; Clima, L.; Pinteala, M. Synergistic Effect of Low Molecular Weight Polyethylenimine and Polyethylene Glycol Components in Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency. Molecules 2019, 24, 1460. https://doi.org/10.3390/molecules24081460

AMA Style

Craciun BF, Gavril G, Peptanariu D, Ursu LE, Clima L, Pinteala M. Synergistic Effect of Low Molecular Weight Polyethylenimine and Polyethylene Glycol Components in Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency. Molecules. 2019; 24(8):1460. https://doi.org/10.3390/molecules24081460

Chicago/Turabian Style

Craciun, Bogdan F., Gabriela Gavril, Dragos Peptanariu, Laura E. Ursu, Lilia Clima, and Mariana Pinteala. 2019. "Synergistic Effect of Low Molecular Weight Polyethylenimine and Polyethylene Glycol Components in Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency" Molecules 24, no. 8: 1460. https://doi.org/10.3390/molecules24081460

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