CELL FUSION–MEDIATED DELIVERY OF BIOMOLECULES FOR GLIOBLASTOMA TREATMENT

Targeted and selective elimination of glioblastoma cells remains a central challenge in neuro-oncology, and existing intracellular drug delivery strategies are limited by low specificity and inefficient manipulation of malignant cells. Here, we present a cell fusion–based delivery platform that exploits the SARS-CoV-2 Spike–hACE2 interaction to enable direct, efficient intercellular transfer of diverse intracellular cargo. This robust cell–cell fusion system supports the delivery of not only soluble proteins but also large subcellular organelles, including mitochondria, the endoplasmic reticulum, and the Golgi apparatus, providing direct cytoplasmic access without the use of viral vectors. Transcriptomic profiling further revealed that fusion-induced cells transition into a non-proliferative state, suggesting an intrinsic regulatory mechanism that adds an additional layer of control over post-fusion cell fate. By integrating optogenetic actuators with the fusion platform, we achieve precise spatiotemporal control over the functions of fused cells and demonstrate selective induction of apoptosis in patient-derived glioblastoma organoids. Together, this non-viral intercellular delivery system establishes cell fusion–mediated transport as a versatile strategy for intracellular biomolecule delivery, functional cellular reprogramming, and precision cancer therapy, offering a new paradigm for targeted glioblastoma treatment.