Glycan-modified cellular nanosponges for enhanced neutralization of botulinum toxin

Summary

This preclinical work strengthens a cell-membrane decoy for botulinum toxin by increasing the abundance of a natural toxin-binding glycan. The researchers metabolically engineered THP-1 cells to express higher levels of gangliosides, then harvested their membranes and wrapped them around synthetic polymer cores. These cellular nanosponges mimic host-cell surfaces encountered by botulinum toxin. Greater ganglioside density produced greater toxin-binding capacity, directly connecting the engineered membrane composition with the intended neutralization mechanism. In vitro, the glycan-enriched particles reduced botulinum-toxin cytotoxicity more effectively than otherwise similar particles made from unmodified membrane. In a mouse intoxication model, they also produced a larger survival benefit when administered after toxin exposure and when used preventively. The principal finding is that metabolic glycan engineering can tune the capture capacity and efficacy of a membrane-coated nanosponge rather than accepting the source membrane as fixed. This provides a modular route to optimizing host-mimicking antidotes and may be relevant to related clostridial toxins. The abstract does not establish binding limits, treatment timing, toxin subtype breadth, chronic safety, immune effects, or comparative efficacy against available antitoxin approaches.