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A Simple Zn2+ Complex-Based Composite System for Efficient Gene Delivery.

Zhe Zhang1, Yanjie Zhao1, Xianggao Meng1

  • 1Key Laboratory of Pesticide and Chemical Biology, Ministry of Education and School of Chemistry, Central China Normal University, Wuhan, 430079, China.

Plos One
|July 20, 2016
PubMed
Summary

Zinc complexes with benzimidazole ligands show potential for gene delivery. Combining them with polyethylene glycol (PEG) and cell-penetrating peptides (CPPs) like TAT significantly enhances DNA nanoparticle cellular uptake and transfection efficiency.

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Area of Science:

  • Coordination Chemistry
  • Nanotechnology
  • Biomaterials

Background:

  • Metal complexes offer advantages for gene delivery, including low cytotoxicity and tunable properties.
  • Benzimidazole-based ligands can form diverse metal complexes with potential gene delivery applications.

Purpose of the Study:

  • To synthesize and characterize Zn2+ complexes with benzimidazole ligands for DNA binding and delivery.
  • To evaluate the gene transfection efficiency and cellular uptake of these complexes, and to improve them using cell-penetrating peptides (CPPs) and polyethylene glycol (PEG).

Main Methods:

  • Synthesis and characterization of ten Zn2+-benzimidazole (bzim) complexes.
  • DNA binding studies to assess complex affinity and DNA condensation.
  • Cellular uptake and transfection efficiency assays, including investigation of endocytosis pathways.

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  • Modification of DNA nanoparticles with TAT(48-60) peptide and PEG.

    • Main Results:

    • Zn2+-bzim complexes demonstrated varying DNA binding affinities, leading to DNA condensation into ~50 nm nanoparticles.
    • Initial transfection efficiency was poor despite low cytotoxicity.
    • Sequential addition of TAT(48-60) and PEG increased nanoparticle size to ~100 nm and enhanced cellular uptake.
    • Clathrin-mediated endocytosis was identified as the primary uptake pathway.
    • The composite system achieved up to 20% of Lipofect's transfection efficiency.

    Conclusions:

    • Zn2+-bzim complexes can form DNA nanoparticles with low toxicity.
    • Combination with PEG and CPPs like TAT significantly improves cellular uptake and transfection efficiency.
    • A simple Zn2+-bzim complex-based composite system shows promise for efficient and low-toxicity gene delivery.