Structure and Composition Define Immunorecognition of Nucleic Acid Nanoparticles.
Structure and Composition Define Immunorecognition of Nucleic Acid Nanoparticles.
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DOI：
10.1021/acs.nanolett.8b01283
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发表时间：
2018-07-11
期刊：
影响因子：
10.8
通讯作者：
Afonin KA
中科院分区：
文献类型：
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作者：
Hong E;Halman JR;Shah AB;Khisamutdinov EF;Dobrovolskaia MA;Afonin KA
核酸纳米颗粒（NANP）已经发展成为一类新的治疗药物，具有检测和治疗疾病的潜力。尽管NANP开发取得了巨大进展，但其免疫毒性（传统治疗性核酸（TNA）临床转化的主要障碍之一）从未得到充分表征。在这里，我们描述了第一次系统地研究了25个代表性的RNA和DNA NANP选择具有不同的设计原理和物理化学性质的免疫识别。我们发现，与传统的TNAs不同，在没有递送载体的情况下使用的NANP是免疫静止的。我们表明，干扰素（IFN）是由NANP触发的关键细胞因子后，他们的吞噬细胞内化，这与预测的基础上与TNAs的经验。然而，除了I型IFN之外，III型IFN还充当NANP的可靠生物标志物，这通常不是TNA的特征。我们表明，整体免疫刺激依赖于NANP的形状，连通性和组成。我们证明，与传统的TNAs一样，浆细胞样树突状细胞是NANP治疗的所有外周血单核细胞中的主要干扰素生产者，清道夫受体介导的摄取和内体Toll样受体信号传导对NANP免疫识别至关重要。然而，陆地资源中心的参与不同于传统的技术需要评估确认所预期的参与。基于这些结果，我们认为NANP技术可以作为与免疫系统通信和调节免疫应答的辅助分子语言的原型。
Nucleic acid nanoparticles (NANPs) have evolved as a new class of therapeutics with the potential to detect and treat diseases. Despite tremendous advancements in NANP development, their immunotoxicity, one of the major impediments in clinical translation of traditional therapeutic nucleic acids (TNAs), has never been fully characterized. Here, we describe the first systematically studied immunological recognition of 25 representative RNA and DNA NANPs selected to have different design principles and physicochemical properties. We discover that, unlike traditional TNAs, NANPs used without a delivery carrier are immunoquiescent. We show that interferons (IFNs) are the key cytokines triggered by NANPs after their internalization by phagocytic cells, which agrees with predictions based on the experiences with TNAs. However, in addition to type I IFNs, type III IFNs also serve as reliable biomarkers of NANPs, which is usually not characteristic of TNAs. We show that overall immunostimulation relies on NANP shapes, connectivities, and compositions. We demonstrate that, like with traditional TNAs, plasmacytoid dendritic cells serve as the primary interferon producers among all peripheral blood mononuclear cells treated with NANPs, and scavenger receptor-mediated uptake and endosomal Toll-like receptor signaling are essential for NANP immunorecognition. The TLR involvement, however, is different from that expected for traditional TNA recognition. Based on these results, we suggest that NANP technology may serve as a prototype of auxiliary molecular language for communication with the immune system and the modulation of immune responses.
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DOI：
10.1016/j.omtn.2017.10.010
发表时间：
2017-12-15
期刊：
Molecular therapy. Nucleic acids
影响因子：
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作者：
Guo S;Li H;Ma M;Fu J;Dong Y;Guo P
通讯作者：
Guo P
用于自动纳米医学的siRNA官能化RNA纳米颗粒的设计和自组装。
影响因子：
14.8
作者：
通讯作者：
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影响因子：
56.9
作者：
Chworos, A;Severcan, I;Jaeger, L
通讯作者：
Jaeger, L
影响因子：
3.5
作者：
Grijalvo S;Alagia A;Jorge AF;Eritja R
通讯作者：
Eritja R
影响因子：
38.3
作者：
通讯作者：
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