Turing miRNA into infinite coordination supermolecule: a general and enabling nanoengineering strategy for resurrecting nuclear acid therapeutics.
Turing miRNA into infinite coordination supermolecule: a general and enabling nanoengineering strategy for resurrecting nuclear acid therapeutics.
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DOI：
10.1186/s12951-021-01212-9
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发表时间：
2022-01-04
影响因子：
10.2
通讯作者：
Liu W
中科院分区：
文献类型：
--
作者：
Li L;He W;You W;Yan J;Liu W
核酸治疗剂的临床转化，特别是那些靶向肿瘤进展的核酸治疗剂，一直受到核酸治疗剂固有弱点的阻碍，包括系统稳定性差、快速清除、膜通透性低和缺乏靶向能力。将小核酸设计成具有结构稳定性和疾病靶向性的无载体纳米药物可能可以克服核酸的药物障碍。建立了一种通过温和、简单的化学反应将治疗性 miRNA 转化为无限金-硫氢基配位超分子 miRNA 的通用方法，称为 IacsRNA，具有近球形纳米结构、高胶体以及抗水解稳定性和低巨噬细胞摄取。与正常 miRNA 相比，IacsRNA 的循环半衰期延长，并且在肿瘤部位积累。此外，Iacs-miR-30c在5次注射剂量的治疗中未表现出对内脏和血液系统的毒性。更重要的是，Iacs-miR-30c在体外和体内有效抑制Wnt信号通路，并有效地敏化结肠癌PDX模型中的5-Fu和黑色素瘤B16F10同种移植模型中的Anti-PD1的效力。总的来说，这项工作充分证实了 IacsRNA 的设计是一种通用且可行的纳米药物策略，可以将脆弱的治疗性 miRNA 转化为潜在的药物。从更广泛的角度来看，miRNA引发的无限协调自组装策略在复兴核酸疗法方面具有明显的优势，可能为包括癌症在内的多种人类疾病的RNA衍生疗法带来新的灵感。在线版本包含可在 10.1186/s12951-021-01212-9 获取的补充材料。
Clinical translation of therapeutic nuclear acid, particularly those targeting tumor progression, has been hampered by the intrinsic weaknesses of nuclear acid therapeutic including poor systemic stability, rapid clearance, low membrane permeability and lack of targeting ability. Small nuclear acid engineered into carrier-free nanodrugs with structural stability and disease targeting may be viable to overcome pharmaceutical obstacles of nuclear acid. A general method through a mild and simple chemistry was established to convert therapeutic miRNA into an infinite Auric-sulfhydryl coordination supramolecular miRNA termed IacsRNA with near-spherical nanostructure, high colloid as well as anti-hydrolysis stability and low macrophage uptakes. IacsRNA presented the increased half-life period in circulation and accumulation at tumor sites in comparison to normal miRNA. Moreover, Iacs-miR-30c showed no toxicity of viscera and sanguis system in the 5-time injection dosage of the treatment. More importantly, Iacs-miR-30c potently suppressed the Wnt signaling pathway in vitro and in vivo, and effectively sensitized both potency of 5-Fu in PDX model of colon cancer and Anti-PD1 in B16F10 homograft model of melanoma. Collectively, this work amply confirmed the design of IacsRNA as a general and viable strategy of nano-pharmaceutic to concert flimsy therapeutic miRNA into potential drugs. Considering from a broader perspective, the miRNA-initiated infinite coordination self-assembly strategy has distinct advantages in resurrecting nuclear acid therapeutics, probably bringing new inspiration to RNA-derived therapeutics of a great variety of human diseases including cancer. The online version contains supplementary material available at 10.1186/s12951-021-01212-9.
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影响因子：
7.2
作者：
Merrill, Bradley J.
通讯作者：
Merrill, Bradley J.
影响因子：
17.1
作者：
Bartneck, Matthias;Keul, Heidrun A.;Groll, Juergen
通讯作者：
Groll, Juergen
影响因子：
8
作者：
Bozzuto G;Molinari A
通讯作者：
Molinari A
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影响因子：
19
作者：
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通讯作者：
Hou, Peng
影响因子：
78.8
作者：
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通讯作者：
Stylianopoulos, Triantafyllos