Extracellular vesicle-based therapeutic strategies for spinal tumors and associated nerve damage: advances, challenges, and future directions

The clinical management of spinal tumors presenting with acute spinal cord compression with consequent neural injury poses two concurrent challenges: achieving oncological control and preserving or restoring neurological function. Surgical decompression and chemoradiotherapy can relieve mechanical compression and reduce tumor burden, but they do not directly restore the damaged neural microenvironment. In recent years, extracellular vesicles (EVs) have emerged as promising cell-free nanotherapeutic candidates. Preclinical evidence suggests that they can cross the blood-spinal cord barrier and deliver functional biomacromolecules. This narrative review critically evaluates recent advances in EV-based interventions for spinal tumors and associated neural injury. To improve interpretive rigor, we distinguish evidence according to translational proximity, from human-derived data and orthotopic spinal tumor models to non-spinal tumor and non-neoplastic spinal cord injury models. We discuss how natural and engineered EVs may improve selective targeting, help overcome chemotherapy resistance, regulate neuroinflammation, and promote axonal regeneration. However, EV therapeutics for spinal tumors remain at an early preclinical stage. In spinal microenvironments that may contain residual tumor cells, EVs can exert double-edged effects, including off-target toxicity, pro-tumorigenic niche remodeling, and enhanced immune evasion. Scalable isolation, purification, and standardized potency assessment under international consensus frameworks remain major barriers. Dedicated tumor-bearing spinal models are therefore required to determine whether EV-based interventions can be developed into safe, viable, and personalized therapeutic approaches.