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FROM:
Preethi L. Chandran (1, 2), Emilios K. Dimitriadis (2), Julianna Lisziewicz (3), Vlad Speransky (2) and Forenc Horkay (1)
(1) Section on Tissue Biophysics and Biomimetics, PPITS, NICHD, National Institutes of Health, Bldg 13, 13 South Drive, Bethesda, USA
(2) Biomedical Engineering and Physical Science Shared Resource, National Institutes of Health, NIBIB, Bldg 13, 13 South Drive, Bethesda, USA
(3) eMMUNITY Inc., 4400 East West Hwy, Bethesda, USA
“DNA nanoparticles with core-shell morphology”, Soft Matter, Vol. 10, No. 38, pp 7653-7660, 2014
DOI: 10.1039/C4SM00908H
ABSTRACT: Mannobiose-modified polyethylenimines (PEI) are used in gene therapy to generate nanoparticles of DNA that can be targeted to the antigen-presenting cells of the immune system. We report that the sugar modification alters the DNA organization within the nanoparticles from homogenous to shell-like packing. The depth-dependent packing of DNA within the nanoparticles was probed using AFM nano-indentation. Unmodified PEI–DNA nanoparticles display linear elastic properties and depth-independent mechanics, characteristic of homogenous materials. Mannobiose-modified nanoparticles, however, showed distinct force regimes that were dependent on indentation depth, with ‘buckling’-like response that is reproducible and not due to particle failure. By comparison with theoretical studies of spherical shell mechanics, the structure of mannobiosylated particles was deduced to be a thin shell with wall thickness in the order of few nanometers, and a fluid-filled core. The shell–core structure is also consistent with observations of nanoparticle denting in altered solution conditions, with measurements of nanoparticle water content from AFM images, and with images of DNA distribution in Transmission Electron Microscopy.
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