Zhang Cheng, Peng Si-Yuan, Hong Sheng, Chen Qi-Wen, Zeng Xuan, Rong Lei, Zhong Zhen-Lin, Zhang Xian-Zheng
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry, Wuhan University, Wuhan, 430072, PR China.
Biomaterials. 2020 Jul;245:119986. doi: 10.1016/j.biomaterials.2020.119986. Epub 2020 Mar 20.
Diabetes is an increasing health problem and associated with inflammatory complications that seriously affects the quality of life and survival of patients. Carbon monoxide (CO), owing to its anti-inflammatory and anti-apoptotic properties, has become a potential therapeutic molecule for the treatment of autoimmune diseases. Here, we constructed a mesoporous silica-based biomimetic CO nanogenerator (mMMn), which was loaded with manganese carbonyl and camouflaged with macrophage membrane. Driven by the active targeting of macrophage membrane to inflammatory sites, the as-designed mMMn could effectively accumulate in pancreatic tissue of type 1 diabetic mice, which was established by consecutive administration of streptozotocin (STZ). It was found that the local reactive oxygen species (ROS) within pancreas could trigger the continuous CO release from mMMn, which greatly ameliorated diabetes in mice with improved blood glucose homeostasis by alleviating inflammatory responses and inhibiting β-cells apoptosis. The exogenous CO targeting to pancreatic tissue paves a novel way for the treatment of type 1 diabetes.
糖尿病是一个日益严重的健康问题,并且与炎症并发症相关,这严重影响患者的生活质量和生存期。一氧化碳(CO)因其抗炎和抗凋亡特性,已成为治疗自身免疫性疾病的一种潜在治疗分子。在此,我们构建了一种基于介孔二氧化硅的仿生CO纳米发生器(mMMn),其负载有羰基锰并用巨噬细胞膜进行伪装。在巨噬细胞膜对炎症部位的主动靶向驱动下,所设计的mMMn能够有效积聚在通过连续注射链脲佐菌素(STZ)建立的1型糖尿病小鼠的胰腺组织中。研究发现,胰腺内的局部活性氧(ROS)可触发mMMn持续释放CO,通过减轻炎症反应和抑制β细胞凋亡,极大地改善了小鼠的糖尿病状况并改善了血糖稳态。外源性CO靶向胰腺组织为1型糖尿病的治疗开辟了一条新途径。