Autor: |
Craciun BF; '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. craciun.bogdan@icmpp.ro., Gavril G; '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. pricope.gabriela@icmpp.ro., Peptanariu D; '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. peptanariu.dragos@icmpp.ro., Ursu LE; '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. ursu.laura@icmpp.ro., Clima L; '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. clima.lilia@icmpp.ro., Pinteala M; '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. pinteala@icmpp.ro. |
Abstrakt: |
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. |