Enhanced Immunostimulatory Activity of Cytosine-Phosphate-Guanosine Immunomodulator by the Assembly of Polymer DNA Wires and Spheres
Enhanced Immunostimulatory Activity of Cytosine-Phosphate-Guanosine Immunomodulator by the Assembly of Polymer DNA Wires and Spheres
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通过聚合物 DNA 线和球的组装增强胞嘧啶-磷酸-鸟苷免疫调节剂的免疫刺激活性
DOI：
10.1021/acsami.9b21075
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发表时间：
2020
影响因子：
9.5
通讯作者：
Liu Xiaoqing
中科院分区：
文献类型：
--
作者：
Yu Wenqian;Sun Junlin;Liu Feng;Yu Shuyi;Xu Zhen;Wang Fuan;Liu Xiaoqing
未甲基化胞嘧啶-磷酸-鸟苷（CpG）寡脱氧核苷酸是一种免疫刺激核酸，广泛用作佐剂或疫苗治疗疾病。然而，目前缺乏一种简单有效的CpG寡脱氧核苷酸递送载体，并具有持久的免疫刺激。本研究通过杂交链反应构建了具有良好生物相容性和免疫刺激活性的CpG基序自组装聚合物丝。设计的聚合物DNA丝作为可编程的多价免疫佐剂，可触发免疫反应，刺激促炎细胞因子分泌，诱导癌细胞凋亡。更引人注目的是，由聚合物DNA线和阳离子聚赖氨酸组装而成的聚合物纳米球进一步提高了细胞摄取，并持续刺激免疫细胞的溶酶体toll样受体9，从而显著增强了免疫细胞的激活。这些结果表明，含有多价CpG的自组装聚合物DNA纳米组件可以引发强烈的免疫反应，并进一步诱导癌细胞死亡。
Unmethylated cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides are immunostimulatory nucleic acids wildly utilized as adjuvants or for vaccines to treat diseases. However, there is a lack of simple and efficient vectors for CpG oligodeoxynucleotide delivery with long-lasting immune stimulation. Herein, self-assembled polymer wires consisting of CpG motifs by hybridization chain reaction were constructed with excellent biocompatibility and immunostimulatory activity. The designed polymer DNA wires acted as programmable multivalent immunoadjuvants and triggered immune response, stimulated pro-inflammatory cytokine secretion, and induced the apoptosis of cancer cells. More strikingly, polymer nanospheres assembled from the polymer DNA wires and cationic poly-l-lysine further improved cellular uptake and continuously stimulate the lysosomal Toll-like receptor 9 of immune cells, thereby remarkably enhancing the activation of immune cells. These results demonstrated that self-assembled polymer DNA nanoassemblies with multivalent CpG could trigger strong immune response and further induce cancer cell death.