Figure 9.

Glycan-modified CNPs for enhanced neutralization of botulinum toxin (BoNT). (A) Schematic illustration of the concept behind modifying CNPs to enhance BoNT neutralization. The study used MΦs as the source cells: un-MΦs (unmodified MΦs), gan-MΦs (MΦs with enhanced glycan expression), un-MΦ-NS (nanosponges coated with membranes of un-MΦs), and gan-MΦ-NS (nanosponges coated with membranes of gan-MΦs). (B) Comparison of GM1 and GT1b expression levels on gan-MΦ-NS and un-MΦ-NS. Gan-MΦ-NS exhibited 2.4-fold higher GM1 and 2.2-fold higher GT1b expressions compared to un-MΦ-NS. (C) The binding capacity of BoNT by nanosponges with the involvement of neuraminidase (NA). BoNT was co-incubated with nanosponges at various concentrations for 30 min, after which the remaining BoNT in the supernatant was collected via centrifugation and measured by ELISA. Gan-MΦ-NS showed accelerated binding, while pretreatment of nanosponges with NA negated the binding ability, confirming the contribution of highly expressed gangliosides to increased binding capacity. (D) In vivo survival rates over 7 days for mice exposed to BoNT at dosages of LD50 or LD100. Injection of gan-MΦ-NS at 100 mg/kg concentration successfully rescued all BoNT-challenged mice at both LD50 and LD100 doses. Adapted with permission from ref (48). Copyright 2023 Elsevier.