CpG oligodeoxynucleotides (CpG ODNs) bind to toll-like receptor 9 (TLR9) and activate the immune system. Thus, CpG ODNs have attracted considerable interest as immunotherapeutic agents or adjuvants for many diseases. Herein we report that polyethylenimine (PEI) functions as a multifunctional vector for both enhancing and regulating the immunostimulatory activity of CpG ODNs. PEI and CpG ODNs formed nanopolyplexes (NPs), which possessed good biocompatibility. PEI-CpG ODN NPs facilitated the internalization of CpG ODNs and induced increasing amounts of cytokines. Most importantly, PEI-CpG ODN NPs induced interleukin-6 (IL-6) and interferon-α (IFN-α) simultaneously, while class B CpG ODNs induced only IL-6. In contrast to class C CpG ODNs, which also simultaneously induce IFN-α and IL-6, the ratio of IFN-α and IL-6 induced by PEI-CpG ODN NPs could be regulated by changing the N/P ratio. This flexible bifurcated cytokine is promising for treating diseases such as cancer that require IL-6 and IFN-α simultaneously. Our findings propose a regulatory effect of PEI on the immunostimulatory activity of CpG ODNs, which will shed light on the development of highly efficient nonviral vectors for CpG ODN-based immunotherapy.

中文翻译：

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聚乙烯亚胺介导的CpG寡脱氧核苷酸传递刺激分叉的细胞因子诱导。

CpG寡脱氧核苷酸（CpG ODN）与toll样受体9（TLR9）结合并激活免疫系统。因此，CpG ODN作为许多疾病的免疫治疗剂或佐剂引起了极大的兴趣。在本文中，我们报道了聚乙烯亚胺（PEI）作为多功能载体，可增强和调节CpG ODN的免疫刺激活性。PEI和CpG ODN形成具有良好生物相容性的纳米复合物（NP）。PEI-CpG ODN NP促进了CpG ODN的内在化，并诱导了细胞因子的增加。最重要的是，PEI-CpG ODN NPs同时诱导白介素6（IL-6）和干扰素-α（IFN-α），而B类CpG ODN仅诱导IL-6。与同时诱导IFN-α和IL-6的C类CpG ODN相比，通过改变N / P比值可以调节PEI-CpG ODN NPs诱导的IFN-α和IL-6的比例。这种灵活的分叉细胞因子有望用于治疗同时需要IL-6和IFN-α的疾病，例如癌症。我们的发现提出了PEI对CpG ODN的免疫刺激活性的调节作用，这将为基于CpG ODN的免疫疗法的高效非病毒载体的开发提供启示。