Mochizuki Shinichi, Miyamoto Noriko, Sakurai Kazuo
Department of Chemistry and Biochemistry, The University of Kitakyushu, 1-1, Hibikino, Wakamatsu-ku, Kitakyushu, Fukuoka, 808-0135, Japan.
Department of Applied Chemistry, Aichi Institute of Technology, 1247, Yachigusa, Yakusacho, Toyota, Aichi, 470-0392, Japan.
Drug Metab Pharmacokinet. 2022 Feb;42:100434. doi: 10.1016/j.dmpk.2021.100434. Epub 2021 Dec 3.
Schizophyllan (SPG), a member of the β-glucan family, can form novel complexes with homo-polynucleotides such as poly(dA) through hydrogen bonding between two main chain glucoses and the one nucleotide base. Dectin-1, one of the major receptors for β-glucans, is known to be expressed on antigen presenting cells (APCs) such as macrophages and dendritic cells. This suggests that the above-mentioned complexes could deliver bound functional oligonucleotides (ODNs) including antisense (AS)-ODNs, small interfering RNA, and CpG-ODNs to the APCs. Analysis using a quartz crystal microbalance revealed that a complex consisting of SPG and dA with a phosphorothioate backbone was recognized by recombinant Dectin-1 protein. Treatment with this complex containing an AS-ODN for tumor necrosis factor alpha protected mice against lipopolysaccharide-induced hepatitis at a very low AS-ODN dose. Moreover, immunization with CpG-ODN/SPG complex and antigenic proteins induced potent antigen specific immune responses. The present review also represents peptide delivery by conjugation with dA and the preparation of a nanogel using DNA-DNA hybridization. These findings indicate that the delivery of a specific ODN using β-glucans could be used for treating various diseases caused by APCs and for activating antigen specific immune responses.
裂褶菌多糖（SPG）是β-葡聚糖家族的一员，它可以通过两条主链葡萄糖与一个核苷酸碱基之间的氢键作用，与同聚核苷酸如聚（dA）形成新型复合物。已知β-葡聚糖的主要受体之一——树突状细胞相关C型凝集素-1（Dectin-1）在巨噬细胞和树突状细胞等抗原呈递细胞（APC）上表达。这表明上述复合物可以将包括反义（AS）-寡核苷酸、小干扰RNA和CpG-寡核苷酸在内的结合功能性寡核苷酸（ODN）递送至APC。使用石英晶体微天平进行的分析表明，由具有硫代磷酸酯主链的SPG和dA组成的复合物可被重组Dectin-1蛋白识别。用含有针对肿瘤坏死因子α的AS-ODN的这种复合物进行治疗，能以非常低的AS-ODN剂量保护小鼠免受脂多糖诱导的肝炎。此外，用CpG-ODN/SPG复合物和抗原性蛋白质进行免疫可诱导强烈的抗原特异性免疫反应。本综述还介绍了通过与dA偶联进行肽递送以及利用DNA-DNA杂交制备纳米凝胶的方法。这些发现表明，使用β-葡聚糖递送特定的ODN可用于治疗由APC引起的各种疾病，并激活抗原特异性免疫反应。
