Hanagata Nobutaka
Nanotechnology Innovation Station, National Institute for Materials Science, Tsukuba, Ibaraki; Graduate School of Life Science, Hokkaido University, Sapporo, Hokkaido, Japan.
Int J Nanomedicine. 2017 Jan 16;12:515-531. doi: 10.2147/IJN.S114477. eCollection 2017.
Unmethylated cytosine-guanine dinucleotide-containing oligodeoxynucleotides (CpG ODNs), which are synthetic agonists of Toll-like receptor 9 (TLR9), activate humoral and cellular immunity and are being developed as vaccine adjuvants to prevent or treat cancers, infectious diseases, and allergies. Free CpG ODNs have been used in many clinical trials implemented to verify their effects. However, recent research has reported that self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes demonstrate higher adjuvant effects than free CpG ODNs, owing to their improved uptake efficiency into cells expressing TLR9. Moreover, protein/peptide-CpG ODN conjugates and nanomaterial-CpG ODN complexes are able to deliver CpG ODNs and antigens (or allergens) to the same types of cells, which enables a higher degree of prophylaxis or therapeutic effect. In this review, the author describes recent trends in the research and development of CpG ODN nanomedicines containing self-assembled CpG ODNs, protein/peptide-CpG ODN conjugates, and nanomaterial-CpG ODN complexes, focusing mainly on the results of preclinical and clinical studies.
含未甲基化胞嘧啶 - 鸟嘌呤二核苷酸的寡脱氧核苷酸（CpG ODNs）是Toll样受体9（TLR9）的合成激动剂，可激活体液免疫和细胞免疫，目前正作为疫苗佐剂进行研发，用于预防或治疗癌症、传染病和过敏症。游离CpG ODNs已在许多临床试验中使用，以验证其效果。然而，最近的研究报告称，自组装CpG ODNs、蛋白质/肽 - CpG ODN缀合物和纳米材料 - CpG ODN复合物表现出比游离CpG ODNs更高的佐剂效果，这是由于它们对表达TLR9的细胞的摄取效率提高。此外，蛋白质/肽 - CpG ODN缀合物和纳米材料 - CpG ODN复合物能够将CpG ODNs和抗原（或过敏原）递送至同一类型的细胞，从而实现更高程度的预防或治疗效果。在这篇综述中，作者描述了含自组装CpG ODNs、蛋白质/肽 - CpG ODN缀合物和纳米材料 - CpG ODN复合物的CpG ODN纳米药物的研发最新趋势，主要关注临床前和临床研究结果。
