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The work reported by Academician Shen Youqing from Zhejiang University, Researcher Xiang Jiajia from Zhejiang University, Researcher Liu Xin from Shao Yi Fu Hospital of Zhejiang University, Professor Fan Shunwu, focuses on the "immune suppression - neural abnormality - bone destruction" triad of intractable diseases associated with bone metastasis. It proposes a highly integrated oxidative response-based nanotherapy strategy. The authors constructed a lipid nanoparticle platform (LipoNCs@pGSDMB) triggered by ROS, which specifically releases STING agonists and GSDMB plasmids in the bone metastasis microenvironment, simultaneously activating innate immunity and inducing immune-induced pyroptosis of immune cells.
Unlike traditional tumor immunotherapy that only focuses on the immune axis, this system further reprograms the expression of calcium channels (VGCC) in tumor cells to cut off the calcium-dependent signal communication between the tumor and sensory nerves, thereby mechanistically disintegrating the "tumor - nerve" positive feedback loop. As a result, in the breast cancer bone metastasis model, nearly complete tumor clearance, disappearance of cancer pain, and bone structure repair were achieved simultaneously.
Overall, this is not a simple "multi-functional superposition" of a nanomedicine, but a oxidative activation-based neuro-immune nanotherapy paradigm targeting the pathological ecological niche, simultaneously reshaping the immune circuit and the neural circuit, providing a conceptual breakthrough for the treatment of bone metastasis and cancer pain. The relevant research, titled "Oxidation-activated nanotherapy boosts tumor immunity and disrupts tumor-nerve crosstalk to combat bone metastases and cancer pain", was published in Science Advances.
Repost:https://mp.weixin.qq.com/s/q_v3E2-WsZOu21Xz6-leAQ
