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.

中文翻译：

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聚合物DNA导线和球体的组装增强了胞嘧啶-磷酸-Guanosine免疫调节剂的免疫刺激活性。

未甲基化的胞嘧啶-磷酸-鸟苷（CpG）寡脱氧核苷酸是免疫刺激性核酸，广泛用作佐剂或用于治疗疾病的疫苗。然而，缺乏用于CpG寡脱氧核苷酸递送并具有持久免疫刺激的简单有效的载体。本文中，通过杂交链反应由CpG基序组成的自组装聚合物线被构建为具有优异的生物相容性和免疫刺激活性。设计的聚合物DNA线充当可编程的多价免疫佐剂并触发免疫反应，刺激促炎性细胞因子分泌，并诱导癌细胞凋亡。更引人注目的是，聚合物纳米球从聚合物DNA导线和阳离子聚组装升-赖氨酸进一步改善细胞摄取并持续刺激免疫细胞的溶酶体Toll样受体9，从而显着增强免疫细胞的活化。这些结果表明，具有多价CpG的自组装聚合物DNA纳米组件可以触发强大的免疫反应，并进一步诱导癌细胞死亡。