Department of Chemistry, Zhejiang University, Hangzhou 310028, China.
Int J Mol Sci. 2019 Apr 28;20(9):2097. doi: 10.3390/ijms20092097.
For decades, macrocyclic compounds have been widely applied in various fields owing to essential physicochemical properties such as their rigid cyclic structures, geometric dimensions (diameter and height), hydrophobic cavity, and hydrophilic interface. This review is an attempt to summarize various research accomplishments involving macrocyclic compounds for drug and gene delivery in immune-modulating therapies: the structures and benefits of main host molecules, their mechanisms regulating the immune system from cell uptake to activation of dendritic cells and T helper lymphocytes, as well as their potential immunotherapy for different diseases. Macrocyclic compounds including cucurbiturils (CBs), calixarenes, pillararenes, cyclodextrins (CyDs), macrocyclic peptides and metallo-supramolecular compounds, have their own unique physicochemical properties and functional derivatizations that enable to improve the biocompatibility, responsiveness to stimuli, and effectiveness of immune-modulating therapy. Based on abundant clarifications of the biological immunity mechanisms, representative constructions of macrocyclic compounds for immune therapies have been conducted for the investigation of treatment of different diseases including cancer, atherosclerosis, Niemann-Pick type C1 disease (NPC1), diabetes, and inflammations. Although there are critical challenges that remain to be conquered, we believe the future of macrocyclic compounds in the immune-modulating therapy must be bright.
几十年来，由于大环化合物具有刚性环状结构、几何尺寸（直径和高度）、疏水性空腔和亲水性界面等重要的物理化学性质，因此被广泛应用于各个领域。本文试图总结涉及大环化合物在免疫调节治疗中的药物和基因传递的各种研究成果：主要主体分子的结构和优势，它们从细胞摄取到树突状细胞和 T 辅助淋巴细胞的激活来调节免疫系统的机制，以及它们在不同疾病中的潜在免疫治疗。大环化合物包括瓜环（CBs）、杯芳烃、柱芳烃、环糊精（CyDs）、大环肽和金属超分子化合物，它们具有独特的物理化学性质和功能衍生化，能够提高免疫调节治疗的生物相容性、对刺激的响应性和有效性。基于对生物免疫机制的充分阐明，已经对用于治疗包括癌症、动脉粥样硬化、尼曼-匹克 C1 病（NPC1）、糖尿病和炎症在内的不同疾病的免疫治疗大环化合物的代表性结构进行了研究。尽管仍然存在需要克服的重大挑战，但我们相信大环化合物在免疫调节治疗中的未来一定是光明的。
