Stroke is the leading neurological cause of death and disability all over the world, with few effective drugs. Nerve growth factor (NGF) is well known for its multifaceted neuroprotective functions post-ischemia. However, the lack of an efficient approach to systemically deliver bioactive NGF into ischemic region hinders its clinical application. In this study, we engineered the exosomes with RVG peptide on the surface for neuron targeting and loaded NGF into exosomes simultaneously, with the resultant exosomes denoted as NGF@Exo RVG . By systemic administration of NGF@Exo RVG , NGF was efficiently delivered into ischemic cortex, with a burst release of encapsulated NGF protein and de novo NGF protein translated from the delivered mRNA. Moreover, NGF@Exo RVG was found to be highly stable for preservation and function efficiently for a long time in vivo . Functional study revealed that the delivered NGF reduced inflammation by reshaping microglia polarization, promoted cell survival, and increased the population of doublecortin-positive cells, a marker of neuroblast. The results of our study suggest the potential therapeutic effects of NGF@Exo RVG for stroke. Moreover, the strategy proposed in our study may shed light on the clinical application of other neurotrophic factors for central nervous system diseases.

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Gluconobacter oxydans, belonging to acetic acid bacteria, is widely used in industrial biotechnology. In our previous study, one of the main glucose metabolic pathways in G. oxydans 621H was blocked by the disruption of the mgdh gene, which is responsible for glucose oxidation to gluconate on cell membrane. The resulting 621H Δmgdh mutant strain showed an enhanced growth and biomass yield on glucose. In order to further understand the intracellular utilization of glucose by 621H Δmgdh, the functions of four fundamental genes, namely glucokinase-encoding glk1 gene, soluble glucose dehydrogenase-encoding sgdh gene, galactose-proton symporter-encoding galp1 and galp2 genes, were investigated. The obtained metabolic characteristics of 621H Δmgdh Δglk1 and 621H Δmgdh Δsgdh double-gene knockout mutants showed that, in vivo, glucose is preferentially phosphorylated to glucose-6-phosphate by glucokinase rather than being oxidized to gluconate by soluble glucose dehydrogenase. In addition, although the galactose-proton symporter-encoding genes were proved to be glucose transporter genes in other organisms, both galp genes (galp 1 and galp2) in G. oxydans were not found to be involved in glucose uptake system, implying that other unknown transporters might be responsible for transporting glucose into the cells.