Cao Xiqian, Mao Lingwei, Tian Yijun, Yan Lang, Geng Bijiang, Zhou Yingtang, Zhu Jiangbo
Department of Health Toxicology, College of Naval Medicine, Naval Medical University, Shanghai, 200433, China.
National Engineering Research Center for Marine Aquaculture, Zhejiang Ocean University, Zhoushan, Zhejiang Province, 316004, China.
J Nanobiotechnology. 2025 Mar 25;23(1):246. doi: 10.1186/s12951-025-03334-w.
Cuproptosis, a novel approach utilizing copper carriers to trigger programmed cell death, exhibits promise for enhancing traditional therapies and activating robust adaptive immune responses. However, the uncontrolled release of Cu ions risks triggering cuproptosis in healthy tissues, potentially causing irreversible damage. To address this, we report on the use of a Cu-MOF (copper metal-organic framework) protective layer to regulate the biodegradation of copper-based nanomaterials. In situ formation of Cu-MOF on CuO nanocubes not only stabilizes the material under physiological conditions but also enhances its sonodynamic therapy (SDT) capabilities by establishing a Z-Scheme heterojunction. Upon SDT activation, the targeted Cu ion release at the tumor site triggers a cascade of reactions, generating reactive oxygen species (ROS) via Fenton-like processes and depleting glutathione (GSH). This ROS surge, combined with effective cuproptosis, modulates the immunosuppressive tumor microenvironment, inducing immunogenic cell death to eliminate primary tumors and inhibit metastasis. This study offers a new paradigm for the controlled integration of SDT, chemodynamic therapy (CDT), cuproptosis, and immunotherapy, achieving precise tumor-targeted treatment via controlled copper nanomaterial degradation.
铜死亡是一种利用铜载体触发程序性细胞死亡的新方法，有望增强传统疗法并激活强大的适应性免疫反应。然而，铜离子的无控释放可能会引发健康组织中的铜死亡，从而可能造成不可逆转的损害。为了解决这个问题，我们报道了使用铜金属有机框架（Cu-MOF）保护层来调节铜基纳米材料的生物降解。在氧化铜纳米立方体上原位形成Cu-MOF不仅能在生理条件下稳定材料，还能通过建立Z型异质结增强其声动力疗法（SDT）能力。在SDT激活后，肿瘤部位的靶向铜离子释放引发一系列反应，通过类芬顿过程产生活性氧（ROS）并消耗谷胱甘肽（GSH）。这种ROS激增与有效的铜死亡相结合，调节免疫抑制性肿瘤微环境，诱导免疫原性细胞死亡以消除原发性肿瘤并抑制转移。本研究为SDT、化学动力疗法（CDT）、铜死亡和免疫疗法的可控整合提供了一种新范式，通过可控的铜纳米材料降解实现精确的肿瘤靶向治疗。
