School of Nano-Tech and Nano Bionics, University of Science and Technology of China, Hefei Anhui 230026, China.
CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano-Bionics, Chinese Academy of Sciences, Suzhou Jiangsu 215123, China.
Biomater Sci. 2022 Sep 27;10(19):5707-5718. doi: 10.1039/d2bm00518b.
The regeneration of myelin sheaths is the ultimate goal of the treatment of demyelination disease, including multiple sclerosis (MS). However, current drugs for MS mainly target the immune system and can only slow down the disease development and do not promote the differentiation of oligodendrocyte precursor cells (OPCs) abundant in the myelin injury region into mature oligodendrocytes to form a new myelin sheath. Brain-derived neurotrophic factor (BDNF) plays an important role in the regulation of OPC proliferation and differentiation into mature oligodendrocytes. Exosomes, a kind of nanoscale membrane vesicle secreted by cells, can be used as potential therapeutic drug delivery vectors for central nervous system diseases. Here, brain-targeted modification and BDNF intracellular-loaded exosomes were produced through engineering HEK293T cells, which can promote the differentiation of OPCs into mature oligodendrocytes . The intranasal administration of the brain-targeted engineered exosome-mediated BDNF was a highly effective delivery route to the brain and had a significant therapeutic effect on remyelination and motor coordination ability improvement in demyelination model mice. The combination of intranasal administration with brain-targeted and BDNF-loaded designed exosomes provides a strategy for efficient drug delivery and treatment of central nervous system diseases.
髓鞘的再生是脱髓鞘疾病治疗的终极目标，包括多发性硬化症（MS）。然而，目前用于 MS 的药物主要针对免疫系统，只能减缓疾病的发展，而不能促进丰富于髓鞘损伤区域的少突胶质前体细胞（OPC）分化为成熟的少突胶质细胞以形成新的髓鞘。脑源性神经营养因子（BDNF）在调节 OPC 增殖和分化为成熟少突胶质细胞方面发挥着重要作用。外泌体是一种由细胞分泌的纳米级膜囊泡，可作为治疗中枢神经系统疾病的潜在治疗药物递送载体。在这里，通过工程化 HEK293T 细胞产生了脑靶向修饰和 BDNF 细胞内负载的外泌体，可促进 OPC 分化为成熟的少突胶质细胞。脑靶向工程外泌体介导的 BDNF 的鼻内给药是一种非常有效的向脑内递药途径，对脱髓鞘模型小鼠的髓鞘再生和运动协调能力改善具有显著的治疗效果。鼻内给药与脑靶向和 BDNF 负载设计的外泌体相结合，为中枢神经系统疾病的高效药物递送和治疗提供了一种策略。
