Institute of Bioengineeringand Nanotechnology (IBN), 31 Biopolis Way, The Nanos, #04-01, 138669, Singapore.
NUS Graduate School for Integrative Sciences & Engineering, National University of Singapore, 117456, Singapore.
Adv Healthc Mater. 2016 Jun;5(11):1272-81. doi: 10.1002/adhm.201600070. Epub 2016 Mar 29.
In this study, a series of star-shaped polycarbonates are synthesized by metal-free organocatalytic ring-opening polymerization of benzyl chloride (BnCl) and mannose-functionalized cyclic carbonate monomers (MTC-BnCl and MTC-ipman) with heptakis-(2,3-di-O-acetyl)-β-cyclodextrin (DA-β-CD) as macroinitiator. The distributions and compositions of pendent benzyl chloride and protected mannose group (ipman) units are facilely modulated by varying the polymerization sequence and feed ratio of the monomers, allowing precise control over the molecular composition, and the resulting polymers have narrow molecular weight distribution. After deprotection of ipman groups and quaternization with various N,N-dimethylalkylamines, these star polymers with optimized compositions of cationic and mannose groups in block and random forms exhibit strong bactericidal activity and low hemolysis. Furthermore, the optimal mannose-functionalized polymer demonstrates mannose receptor-mediated intracellular bactericidal activity against BCG mycobacteria without inducing cytotoxicity on mammalian cells at the effective dose. Taken together, the materials designed in this study have potential use as antimicrobial agents against diseases such as tuberculosis, which is caused by intracellular bacteria.
在这项研究中，通过无金属有机催化开环聚合，以七（2,3-二-O-乙酰基）-β-环糊精（DA-β-CD）为大分子引发剂，合成了一系列星型聚碳酸酯。通过改变聚合顺序和单体进料比，可以方便地调节支化的苄基氯和保护的甘露糖单元（ipman）的分布和组成，从而可以精确控制分子组成，所得聚合物具有较窄的分子量分布。脱保护 ipman 基团并与各种 N,N-二甲基烷基胺季铵化后，这些具有嵌段和无规形式的优化阳离子和甘露糖基团组成的星型聚合物表现出很强的杀菌活性和低溶血活性。此外，最佳的甘露糖功能化聚合物在有效剂量下对哺乳动物细胞没有细胞毒性，却表现出对 BCG 分枝杆菌的甘露糖受体介导的细胞内杀菌活性。综上所述，本研究设计的材料具有作为抗分枝杆菌药物的潜力，分枝杆菌可引起结核病等疾病。
