Genetically Engineered Glycosylphosphatidylinositol-Anchored Anti-GD2 Nanobody-Exosome Mimetics for Targeted Osteosarcoma Therapy In Vitro and In Vivo

This study focuses on the engineering of exosome mimetics (EMs) that are decorated with an antidisialoganglioside (GD2) nanobody for targeting osteosarcoma. We engineer the anti-GD2 nanobody coding vector into HEK-293T (293T) cells and fuse it with the decay-accelerating factor (DAF)-derived glycosylphosphatidylinositol (GPI) anchor signal peptide. The sequential extrusion method was used to produce the targeted EMs. These engineered GD2-targeted EMs (GD2-EMs) possess the same exosome markers as regular exosomes, are produced in large quantities, have a nanoscale size, and feature a surface anti-GD2 nanobody. Furthermore, they demonstrate increased internalization in osteosarcoma cells compared to unmodified EMs. In animal experiments using nude mice, the GD2-EMs exhibited superior tumor targeting, confirming their efficacy in vivo. In conclusion, the study successfully engineered anti-GD2 EMs, which showed promising results as a drug delivery system for osteosarcoma, indicating that engineering anti-GD2 EMs may be a viable approach for combating this disease.