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Lysosomal Rupture-Mediated “Broken Window Effect” to Amplify Cuproptosis and Pyroptosis for High-Efficiency Cancer Immunotherapy
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2024-02-23 , DOI: 10.1002/adfm.202400496 Guoqing Zhu 1 , Man Wang 1 , Luying Qiao 1 , Yulin Xie 1 , Junrong Wang 1 , Lei Li 1 , Qianqian Sun 1 , Pan Zheng 2 , Chunxia Li 1
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2024-02-23 , DOI: 10.1002/adfm.202400496 Guoqing Zhu 1 , Man Wang 1 , Luying Qiao 1 , Yulin Xie 1 , Junrong Wang 1 , Lei Li 1 , Qianqian Sun 1 , Pan Zheng 2 , Chunxia Li 1
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Autophagy, a lysosome-involved degradation pathway, as a self-protective cellular process, always weakens the efficiency of tumor therapies. Herein, for the first time, the biodegradable copper (Cu) ions doped layered double hydroxide (Cu-LDH) nanoparticles are reported for cancer immunotherapy via lysosomal rupture-mediated “Broken Window Effect”. Only injection of Cu-LDH single therapeutic agent achieves various organelles destruction after lysosomal rupture, as well as the abnormal aggregation of Cu ions in tumor cells for cuproptosis and pyroptosis. More importantly, autophagy inhibition caused by lysosomal rupture improves Cu ions overload-mediated cuproptosis and pyroptosis by blocking the lysosome-mediated bulk degradation pathway, leading to good anti-tumor immune responses and ultimately high-efficiency tumor growth inhibition. This lysosomal rupture-mediated “Broken Window Effect” provides a new paradigm for the autophagy enhanced tumor therapy.
中文翻译：
溶酶体破裂介导的“破窗效应”放大铜垂和焦亡以实现高效癌症免疫治疗
自噬是一种溶酶体参与的降解途径，作为一种自我保护的细胞过程，总是会削弱肿瘤治疗的效率。在此，首次报道了可生物降解的铜（Cu）离子掺杂的层状双氢氧化物（Cu-LDH）纳米颗粒通过溶酶体破裂介导的“破窗效应”用于癌症免疫治疗。仅注射Cu-LDH单一治疗剂即可实现溶酶体破裂后多种细胞器的破坏，以及肿瘤细胞内Cu离子的异常聚集，导致铜凋亡和焦亡。更重要的是，溶酶体破裂引起的自噬抑制通过阻断溶酶体介导的大量降解途径，改善铜离子超载介导的铜凋亡和焦亡，从而产生良好的抗肿瘤免疫反应，最终实现高效的肿瘤生长抑制。这种溶酶体破裂介导的“破窗效应”为自噬增强肿瘤治疗提供了新的范例。
更新日期：2024-02-23
中文翻译：
溶酶体破裂介导的“破窗效应”放大铜垂和焦亡以实现高效癌症免疫治疗
自噬是一种溶酶体参与的降解途径，作为一种自我保护的细胞过程，总是会削弱肿瘤治疗的效率。在此，首次报道了可生物降解的铜（Cu）离子掺杂的层状双氢氧化物（Cu-LDH）纳米颗粒通过溶酶体破裂介导的“破窗效应”用于癌症免疫治疗。仅注射Cu-LDH单一治疗剂即可实现溶酶体破裂后多种细胞器的破坏，以及肿瘤细胞内Cu离子的异常聚集，导致铜凋亡和焦亡。更重要的是，溶酶体破裂引起的自噬抑制通过阻断溶酶体介导的大量降解途径，改善铜离子超载介导的铜凋亡和焦亡，从而产生良好的抗肿瘤免疫反应，最终实现高效的肿瘤生长抑制。这种溶酶体破裂介导的“破窗效应”为自噬增强肿瘤治疗提供了新的范例。
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