(182d) Glycan-Modified Cellular Nanosponges for Enhanced Neutralization of Botulinum Toxin

Botulinum toxin (BoNT) is a potent protein neurotoxin that disrupting neural transmission by inhibiting the release of neurotransmitter. The toxin has been found in medical applications. Its characteristics make it a potential bioterrorist weapon, which threatens public health. Currently, there is a lack of effective antidote for BoNT in the event of a biological attack. Here, we propose a novel solution with cell membrane coating nanotechnology. The glycan modified cellular nanosponges, developed via metabolic engineering, acted as cell decoys to bind with BoNT for detoxification. To prepare the nanosponges, we first increased the expression levels of gangliosides on THP-1 cells through metabolic engineering. Then, nanosponges were made by coating the modified THP-1 cell membrane onto synthetic polymeric cores. Our findings showed that increased levels of gangliosides were expressed on the cellular nanosponges, leading to higher binding capacities with BoNT. Therefore, the glycan-modified cellular nanosponges exhibit superior efficacy in neutralizing BoNT in a synaptic vesicle recycling assay when compared to their unmodified counterparts. In a mouse model of BoNT intoxication, the glycan-modified cellular nanosponges showed survival benefits when administered both as a treatment and a preventative regimen. These results highlight the potential of cellular nanosponges, especially when modified with glycans, as a promising platform against BoNT and related clostridial toxins.