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Fluorescent labeling of plasmid DNA for gene delivery: Implications of dye hydrophobicity on labeling efficiencies and nanoparticle size
Journal article   Open access   Peer reviewed

Fluorescent labeling of plasmid DNA for gene delivery: Implications of dye hydrophobicity on labeling efficiencies and nanoparticle size

Nathan A. Delvaux, Basil Mathew and Kevin G. Rice
Analytical biochemistry, Vol.644, pp.113895-113895
05/01/2022
DOI: 10.1016/j.ab.2020.113895
PMCID: PMC7870724
PMID: 32783899
url
https://www.ncbi.nlm.nih.gov/pmc/articles/7870724View
Open Access

Abstract

Covalent fluorescent labels are important tools for monitoring the in vitro and in vivo localization of plasmid DNA nanoparticles, but must meet several criteria including high DNA labeling efficiencies and minimal impact on nanoparticle size. We developed a novel fluorescent labeling strategy utilizing an aryl azide photolabel conjugated to a short cationic peptide to label plasmid DNA with Cyanine 5 and sulfo-Cyanine 5. Using a simple camera flash apparatus, photolabel-peptide-dyes can be conjugated to DNA in minutes with preservation of DNA structure and minimal dye photobleaching. The addition of two anionic sulfonates to the Cyanine 5 core greatly improved labeling efficiencies from -13 to -53% and mitigated PEGylated polyacridine peptide-DNA nanoparticle size increases over a range of labeling densities. Comparison of our sulfo-Cyanine 5 peptide label to the Mirus Bio Label IT-Cy5 kit revealed that while both did not affect nanoparticle sizes appreciably, labeling efficiencies with our conjugate were higher, possibly due to the higher positive charge density on the peptide linker. The results from this work provide important considerations for choosing fluorophore tags to track DNA nanoparticles.
Biochemical Research Methods Biochemistry & Molecular Biology Chemistry Chemistry, Analytical Life Sciences & Biomedicine Physical Sciences Science & Technology

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