Original: https://doi.org/10.1016/j.mtbio.2025.102496
Neuroblastoma is a difficult childhood cancer to treat because current therapies are limited, often stop working, and can cause serious side effects. In this study, we created a new nanodrug delivery system that targets a protein called CD24 on neuroblastoma cells and delivers two components—cystine and glucose oxidase (GOx)—to trigger a special type of cell death called disulfidptosis.
First, we made exosome-mimicking vesicles (EM-CD24). To do this, we engineered HEK-293T cells to produce vesicles that display an anti-CD24 nanobody on their surface, using a GPI anchor signal to attach the nanobody. We then processed these cells to form vesicles that look and behave like natural exosomes but can be produced in large quantities. Because they carry anti-CD24 nanobodies, these vesicles can specifically target tumor cells that express CD24.
We discovered that cystine normally helps cancer cells grow, but when glucose is low, cystine instead triggers disulfidptosis—a harmful process for the tumor cells. Based on this, we built a redox-responsive nanoplatform called Cys-hMnO2@GOx@EM-CD24. This system loads cystine and GOx into hollow manganese dioxide nanoparticles and then wraps them inside the CD24-targeting vesicles.
This targeted system allows more drug to accumulate in the tumor, lowers the cancer cells’ NADPH levels, and activates cystine-driven disulfidptosis. As a result, it effectively blocked the growth of both primary and metastatic tumors, while causing very little harm to the rest of the body.
Overall, this study shows that CD24-targeted, environment-responsive nanomedicine can take advantage of cancer cell metabolism and may offer a promising new treatment option for neuroblastoma.