Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency

This article is associated with the MDPI-Molecules, “Synergistic Effect of Low Molecular Weight Polyethylenimine and Polyethylene Glycol Components in Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency” doi.org/10.3390/molecules24081460.

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Created by: Mariana Pinteala

Revised by: Lilia Clima

In his pioneering book “Constitutional Dynamic Chemistry” [1], J. M. Lehn (Nobel Prize in supramolecular chemistry) explained that the new paradigm Constitutional Dynamic Chemistry (CDC) is in fact a “bridge” connecting Supramolecular Chemistry and Adaptive Chemistry, covering both the molecular and supramolecular levels. CDC takes place when the molecular assemblies (containing covalent bonds) could form and breakdown in a reversible mode (allows a continuous change) by reorganization and exchange of building blocks. [2][3][4][5]

In this context, researchers who work at the interface of biomaterials, gene therapy and drug delivery took into consideration the CDC paradigm and have identified several design parameters for the non-viral vectors to perform optimum delivery of biologically active material into cells. Dynamic approaches allow for the simple generation of large chemical libraries from sets of building blocks, based on reversible exchanges between the components. Moreover, thus designed and prepared molecular and supramolecular libraries can adapt to the system constraints, for example, allowing selection events driven by molecular recognition and self-assembly or in response to external stimuli.

Progress has been recently made to the field [6][7][8][9][10][11], including our group where we herein report the synergy between components in dynamic combinatorial frameworks (DCFs) formed by connecting PEGylated squalene (SQ-PEG-NH2), poly-(ethyleneglycol)-bis(3-aminopropyl) (NH2-PEG-NH2) and low molecular weight polyethylenimine (PEI) components to 1,3,5-benzenetrialdehyde (TA), via reversible imine bond, applying a dynamic combinatorial chemistry approach (Figure 1). 

Figure 1. DCF concept for the formation of dynamic combinatorial nonviral vectors.

Comparative structural and morphological data, DNA binding affinity, toxicity and transfection efficiency concerning the ratio of PEI and presence or absence of NH2-PEG-NH2 in composition of dynamic combinatorial frameworks were taken into consideration. In vitro biological assessments have revealed the importance of the DCFs components ratio: DCF vectors containing NH2-PEG-NH2 and the lowest amount of PEI have significant transfection efficiency at N/P 50 ratio and display insignificant cytotoxicity on the HeLa cell line.

The investigated DCF approach in changing and testing the components for the improved transfection effect of DCF nonviral vectors, open a vast possibility in optimizing the structure of DCF by easy exchange of components. For example, we intend to also investigate the incorporation and testing of DCFs with PEG moieties of different sizes, exchange of linear and branched PEI of different sizes and last, but not least, the nature of the core molecule.

This work was supported by Horizon 2020 WIDESPREAD 2-2014: ERA Chairs Project no 667387 and a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS/CCCDI – UEFISCDI, project number PN-III-P3-3.6-H2020- 2016-0011, within PNCDI III.

References

  1. J.M. Lehn. Constitutional Dynamic Chemistry: Bridge from Supramolecular Chemistry to Adaptive Chemistry. In Constitutional Dynamic Chemistry; Barboiu, M., Eds.; Ed. Springer: Berlin, Heidelberg,, 2012; pp. 1-32.
  2. J.M. Lehn. Supramolecular chemistry: concepts and perspectives; Wiley, Eds.; VCH: Weinheim, 1995; pp. 1-281.
  3. Jean-Marie Lehn; Dynamers: dynamic molecular and supramolecular polymers. Progress in Polymer Science 2005, 30, 814-831, 10.1016/j.progpolymsci.2005.06.002.
  4. Williams G. Skene; Jean-Marie P. Lehn; J.-M. P. Lehn; Dynamers: Polyacylhydrazone reversible covalent polymers, component exchange, and constitutional diversity. Proceedings of the National Academy of Sciences 2004, 101, 8270-8275, 10.1073/pnas.0401885101.
  5. Jean-Marie Lehn; Toward complex matter: Supramolecular chemistry and self-organization. Proceedings of the National Academy of Sciences 2002, 99, 4763-4768, 10.1073/pnas.072065599.
  6. Romina Catana; Ioana Moleavin; Lilia Clima; Alexandru Rotaru; Elena-Laura Ursu; Mariana Pinteala; Mihail Barboiu; Dynamic constitutional frameworks for DNA biomimetic recognition. Chemical Communications 2015, 51, 2021-2024, 10.1039/C4CC07525K.
  7. Lilia Clima; Dragos Peptanariu; Mariana Pinteala; Adrian Salic; Mihail Barboiu; DyNAvectors: dynamic constitutional vectors for adaptive DNA transfection. Chemical Communications 2015, 51, 17529-17531, 10.1039/C5CC06715D.
  8. Ioana-Andreea Turin-Moleavin; Florica Doroftei; Dragos Peptanariu; Mariana Pinteala; Adrian Salic; Adina Coroaba; Mihail Barboiu; Dynamic constitutional frameworks (DCFs) as nanovectors for cellular delivery of DNA. Organic & Biomolecular Chemistry 2015, 13, 9005-9011, 10.1039/C5OB01315A.
  9. Geta David; Lilia Clima; Manuela Calin; Cristina Ana Constantinescu; Mihaela Balan-Porcarasu; Cristina Mariana Uritu; Bogdan C. Simionescu; Squalene/polyethylenimine based non-viral vectors: synthesis and use in systems for sustained gene release. Polymer Chemistry 2018, 9, 1072-1081, 10.1039/c7py01720k.
  10. Bogdan Florin Craciun; Gabriela Gavril; Dragos Peptanariu; Laura Elena Ursu; Lilia Clima; Mariana Pinteala; Synergistic Effect of Low Molecular Weight Polyethylenimine and Polyethylene Glycol Components in Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency. Molecules 2019, 24, 1460, 10.3390/molecules24081460.
  11. Lilia Clima; Elena L. Ursu; Mariana Pinteala; Alexandru Rotaru; Corneliu Cojocaru; Mihail Barboiu; Experimental design, modeling and optimization of polyplex formation between DNA oligonucleotides and branched polyethylenimine. Organic & Biomolecular Chemistry 2015, 13, 9445-9456, 10.1039/C5OB01189B.

Cite this article

Lilia, Clima; Mariana, Pinteala. Dynamic Nonviral Vector Structure, Toxicity, and Transfection Efficiency, Encyclopedia, 2019, v2, Available online: https://encyclopedia.pub/154