ArticleScience advances2026
Oxidation-activated nanotherapy boosts tumor immunity and disrupts tumor-nerve crosstalk to combat bone metastases and cancer pain.
Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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14 authors.
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Abstract
Bone metastasis remains a formidable challenge in oncology due to the interdependent triad of immunosuppression, neuropathic pain, and osteolytic destruction. Current treatments fail to holistically address these pathophysiological axes. Here, we develop a reactive oxygen species (ROS)-responsive liposomal nanoplatform (LipoNCs@pGSDMB) that codelivers a polymeric stimulator of interferon genes (STING) agonist and a gasdermin B (GSDMB) plasmid for dual neuro-immune modulation. Upon tumor-selective activation in metastatic bone niches, this nanotherapy induces STING-driven immune priming and GSDMB-mediated pyroptosis, triggering potent antitumor responses. Crucially, LipoNCs@pGSDMB restore voltage-gated calcium channel (VGCC) expression in tumor cells, a prognostic biomarker identified through multiomics analysis of clinical specimens, thereby blocking calcium-dependent neurosignaling and disrupting prometastatic tumor-nerve cross-talk. In breast cancer bone metastasis models, this approach achieves 94% tumor suppression, complete pain resolution, and efficient bone restoration. By converging oxidation-responsive nanomaterial engineering, immunomodulation, and neural circuit reprogramming, this work establishes a paradigm-shifting neuroimmunotherapy platform that dismantles the self-reinforcing metastasis niche while addressing its debilitating sequelae.
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