Controlled Release of a Dual Zinc-Sensing and Gene Regulating Small Molecule from DNA Micelles

Intracellular zinc ions are essential for various biological cell processes and are often dysregulated in many diseases de-pending on their location, protein binding affinity, and concentration in the cell. Due to their prevalence in diseases, it is important to not only effectively sense but chelate the often excess amount of zinc in a cell to alleviate further disease progression. N, N, N', N'-tetrakis (2-pyridinylmethyl)-1,2-ethanediamine (TPEN) is a selective zinc chelator but its water-insoluble nature and general cytotoxicity limit its therapeutic potential. To address these challenges, TPEN loaded nucleic acid nanocapsules (TL-NANs) were synthesized, and its dual ability to sense and suppress zinc levels intracellularly were evaluated. Additionally, TL-NANs were incubated in lung cells and shown to down regulate Eotaxin, a protein up-regulated during asthma, at significantly reduced concentrations of TPEN showcasing the therapeutic potential of this drug for asthma.