Authors:

Keith S Yung

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About Paper:

A major limitation for delivering therapeutics to the brain to treat neurodegenerative diseases is the Blood-Brain Barrier (BBB), a highly selective permeable layer of cells. While the BBB is effective in achieving brain homeostasis, it remains an obstacle for many engineered nanoparticles to deliver cargo ., Tetrahedral DNA nanostructures (TDNs) have demonstrated their potential for delivering across physiological barriers, including the BBB, due to their biocompatibility, stability, exact sizing, and simple assembly. In our work, we designed and optimized yield of a large-scale tetrahedral DNA nanostructure with two double helices per edge and six full turns between vertices as a drug delivery vehicle. The enlarged TDN allows for reliable and higher concentration drug loading, such as miRNA or doxorubicin, when compared to other commonly used smaller TDNs. Yield optimization was achieved through testing different buffers, annealing regimes, DNA concentrations, circularized vs uncircularized strands, and molar ratios using native polyacrylamide gel electrophoresis. Our results indicate that the large- scale TDN assembles at approximately 25% yield using 500 nM DNA, 12.5 mM magnesium acetate in 1× TAE buffer, and a 1:4:3 ratio of the circularized strand to strands 2 and 3 mixed and slow annealed over two days. These findings establish a strong foundation for the use of these TDNs in targeted neurological drug delivery. Keywords: DNA Nanomaterials; Drug Delivery; Blood-Brain Barrier; Nanoparticle Assembly; Neurodegenerative Disease

Source:

Purdue University / 2025

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Co-authors:

Keith S Yung