Dynamically adaptive soft bioelectronics for neuro-immunomodulatory cancer therapy

Abstract Many solid tumors remain refractory to immunotherapy due to profoundly immunosuppressive tumor microenvironments. Although vagus nerve stimulation offers a direct neural axis to reprogram immune function, its potential in cancer immunotherapy remains unrealized due to the absence of stable, system-level neuromodulation platforms. Herein, we develop a miniature subdiaphragmatic vagus nerve stimulator (SVNS) for near-organ neuromodulation of pancreatic tumor immunity. To construct stable electrical coupling with subdiaphragmatic vagus nerve (SVN) along the esophagus, a dynamically adaptive neural interface comprising an injectable anti-fatigue adhesive conductive hydrogel and a deformable liquid metal electrode is explored. The SVNS is integrated with a battery-free lead-free wireless power module, which can be configured into a Swiss-roll architecture, enabling minimally invasive implantation. In an orthotopic mouse model of pancreatic tumor, chronic SVN stimulation using SVNS suppressed tumor growth and metastasis, reshaped tumor innervation, promoted a shift toward an M1-like TAM phenotype, enhanced cytotoxic immune cell infiltration, and further potentiated the efficacy of anti-PD-1 immunotherapy.