期刊
ACS NANO
卷 15, 期 3, 页码 4394-4404出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.0c07915
关键词
DNA; DNA nanotechnology; bilayer membrane; white blood cells; lipids; immunomodulation; nanostructures
类别
资金
- Academy of Medical Sciences
- BBSRC [BB/N017331/1, BB/MO09513/1]
- Leverhulme Trust [RPG2017-015]
- National Physical Laboratory
- NIRH
- BBSRC [BB/N017331/1] Funding Source: UKRI
DNA nanotechnology produces precision nanostructures of defined chemistry, which can function as vaccines by selectively binding with white blood immune cells via membrane anchors, showing potential advantages in serum stability and immune modulation.
DNA nanotechnology produces precision nanostructures of defined chemistry. Expanding their use in biomedicine requires designed biomolecular interaction and function. Of topical interest are DNA nanostructures that function as vaccines with potential advantages over nonstructured nucleic acids in terms of serum stability and selective interaction with human immune cells. Here, we describe how compact DNA nanobarrels bind with a 400-fold selectivity via membrane anchors to white blood immune cells over erythrocytes, without affecting cell viability. The selectivity is based on the preference of the cholesterol lipid anchor for the more fluid immune cell membranes compared to the lower membrane fluidity of erythrocytes. Compacting DNA into the nanostructures gives rise to increased serum stability. The DNA barrels furthermore functionally modulate white blood cells by suppressing the immune response to pro-inflammatory endotoxin lipopolysaccharide. This is likely due to electrostatic or steric blocking of toll-like receptors on white blood cells. Our findings on immune cell-specific DNA nanostructures may be applied for vaccine development, immunomodulatory therapy to suppress septic shock, or the targeting of bioactive substances to immune cells.
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