DNA Nanodevices with Selective Immune Cell Interaction and Function
DNA Nanodevices with Selective Immune Cell Interaction and Function
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DOI：
10.1021/acsnano.0c07915
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发表时间：
2021-01-25
期刊：
影响因子：
17.1
通讯作者：
Howorka, Stefan
中科院分区：
文献类型：
--
作者：
Arulkumaran, Nishkantha;Lanphere, Conor;Howorka, Stefan
DNA纳米技术产生精确的纳米结构的定义化学。扩大它们在生物医学中的应用需要设计生物分子的相互作用和功能。当前关注的是作为疫苗的DNA纳米结构，它在血清稳定性和与人体免疫细胞的选择性相互作用方面比非结构化核酸具有潜在优势。在这里，我们描述了紧凑的DNA纳米管是如何通过膜锚点以400倍的选择性结合到白细胞免疫细胞而不是红细胞上，而不影响细胞活力的。这种选择性是基于胆固醇脂质锚点对流动性更强的免疫细胞膜的偏好，而红细胞的细胞膜流动性较低。将DNA压缩到纳米结构中可以提高血清的稳定性。DNA桶进一步通过抑制对促炎内毒素脂多糖的免疫反应来功能调节白细胞。这可能是由于白细胞上toll样受体的静电或位阻。我们关于免疫细胞特异性DNA纳米结构的发现可能应用于疫苗开发、抑制感染性休克的免疫调节治疗或生物活性物质靶向免疫细胞。
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.