Controlled Release of a Dual Zinc‐Sensing and Gene Regulating Small Molecule from DNA Micelles
Controlled Release of a Dual Zinc‐Sensing and Gene Regulating Small Molecule from DNA Micelles
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DNA 胶束中双锌传感和基因调节小分子的受控释放
DOI：
10.1002/cbic.202300189
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发表时间：
2023
期刊：
影响因子：
3.2
通讯作者：
Rouge, Jessica L.
中科院分区：
文献类型：
--
作者：
Sawant, Shraddha S.;Gudipati, Saketh;Veczko, Samantha R.;Rouge, Jessica L.
细胞内锌离子对于各种生物细胞过程是必需的，并且在许多疾病中经常失调，这取决于它们在细胞中的位置、蛋白质结合亲和力和浓度。由于它们在疾病中的流行，重要的是不仅要有效地检测，而且要螯合细胞中经常过量的锌，以减轻进一步的疾病进展。N，N，N′，N′-四（2-吡啶基甲基）-1，2-乙二胺（TPEN）是一种选择性锌螯合剂，但其水不溶性和一般细胞毒性限制了其治疗潜力。为了解决这些挑战，合成了负载TPEN的核酸纳米帽（TL-NAN），并评估了其感测和抑制细胞内锌水平的双重能力。此外，TL-NAN在肺细胞中孵育，并显示在显著降低的TPEN浓度下下调Eotaxin，Eotaxin是一种在哮喘期间上调的蛋白质，显示了这种药物对哮喘的治疗潜力。
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.