The efficacy of transarterial chemoembolization(TACE)has been limited by insufficient embolization and a high incidence of tumor recurrence.Herein,we iden-tified that aberrant metabolic reprogramming and immunosuppressio...The efficacy of transarterial chemoembolization(TACE)has been limited by insufficient embolization and a high incidence of tumor recurrence.Herein,we iden-tified that aberrant metabolic reprogramming and immunosuppression contribute to TACE refractoriness and Rhein,as a potential glycolytic metabolism inhibitor and immunoactivation inducer,was optimized to sensitize tumors to TACE therapy.To achieve efficient embolization,we developed an oil-in-water lipiodol embolic emulsion by stabilizing the self-assembled Rhein nanogel.The assembled Rhein exhibited a nanofiber network,and its integration enhanced the mechanical stability and viscoelasticity of the lipiodol embolic agent.With the synergistic advantages of solid and liquid embolic agents,this carrier-free Pickering emulsion exhibits effi-cient embolization and sustained drug release in models of unilateral renal artery embolization,rabbit ear tumor embolization,rabbit orthotopic liver cancer,and rat orthotopic liver cancer.Compared to conventional three-way catheter mixing meth-ods,multimodal imaging corroborates a marked enhancement in local drug retention and tumor suppression.Importantly,the incorporation of Rhein-mediated syner-gistic immunoembolization in this strategy achieved efficient embolization while robustly activating anti-tumor immune responses,including inducing immunogenic cell death,dendritic cell activation,and major histocompatibility complex class I pre-sentation to CD8+T cells for tumor killing.Together,thesefindings reveal a novel strategy for the application of self-assembled Rhein nanofiber-stabilized lipiodol emulsion to control metabolic signaling and immunoactivation in TACE.展开更多
基金Major State Basic Research Development Program of China,Grant/Award Number:2023YFB3810000National Natural Science Foundation of China,Grant/Award Numbers:U22A20333,81925019,U1705281,82202330+2 种基金Fundamental Research Funds for the Central Universities,Grant/Award Numbers:20720190088,20720200019Science Foundation of Fujian Province,Grant/Award Number:2020Y4003Program for New Century Excellent Talents in University,China,Grant/Award Number:NCET-13-0502。
文摘The efficacy of transarterial chemoembolization(TACE)has been limited by insufficient embolization and a high incidence of tumor recurrence.Herein,we iden-tified that aberrant metabolic reprogramming and immunosuppression contribute to TACE refractoriness and Rhein,as a potential glycolytic metabolism inhibitor and immunoactivation inducer,was optimized to sensitize tumors to TACE therapy.To achieve efficient embolization,we developed an oil-in-water lipiodol embolic emulsion by stabilizing the self-assembled Rhein nanogel.The assembled Rhein exhibited a nanofiber network,and its integration enhanced the mechanical stability and viscoelasticity of the lipiodol embolic agent.With the synergistic advantages of solid and liquid embolic agents,this carrier-free Pickering emulsion exhibits effi-cient embolization and sustained drug release in models of unilateral renal artery embolization,rabbit ear tumor embolization,rabbit orthotopic liver cancer,and rat orthotopic liver cancer.Compared to conventional three-way catheter mixing meth-ods,multimodal imaging corroborates a marked enhancement in local drug retention and tumor suppression.Importantly,the incorporation of Rhein-mediated syner-gistic immunoembolization in this strategy achieved efficient embolization while robustly activating anti-tumor immune responses,including inducing immunogenic cell death,dendritic cell activation,and major histocompatibility complex class I pre-sentation to CD8+T cells for tumor killing.Together,thesefindings reveal a novel strategy for the application of self-assembled Rhein nanofiber-stabilized lipiodol emulsion to control metabolic signaling and immunoactivation in TACE.
