天津大学最新Cell子刊：开发新型铜死亡癌症疗法

Core Viewpoint - Copper is an essential element for life, playing a critical role as a cofactor in various enzymatic processes. The discovery of cuproptosis, a new form of programmed cell death linked to copper ion homeostasis, presents significant implications for cancer therapy [1][2]. Group 1: Copper and Cuproptosis - Copper is a vital trace element in human life, necessary for various biological functions, but can become toxic at elevated levels, leading to cell death [1]. - Cuproptosis, identified in 2022, is characterized by the disruption of copper ion homeostasis and abnormal regulation of protein acylation, resulting in unique cell death pathways [1]. Group 2: Research and Development - A research team from Tianjin University published a study on July 11, 2025, focusing on a covalent organic framework designed to induce intracellular copper accumulation for cuproptosis cancer therapy [3]. - The study developed a nano-system, P1+P2@COF@F127-D, which utilizes endogenous copper to achieve copper-based cancer treatment through a cascade reaction [6]. Group 3: Mechanism of Action - The nano-system initiates a cascade reaction by introducing a copper output inhibitor, DC_AC50, which specifically increases intracellular levels of cuprous ions (Cu+) in cancer cells, leading to irreversible cuproptosis [6][10]. - The system employs small molecule inhibitors of glutaminase-1 (GLS1) encapsulated in a glutathione-responsive covalent organic framework, facilitating the release of DC_AC50 and the GLS1 inhibitors upon cellular uptake [7]. Group 4: Highlights of the Study - The research successfully developed a copper death therapy nano-system that does not require exogenous copper, instead utilizing endogenous copper to trigger a copper-glutathione-mediated intracellular cascade reaction, amplifying the anti-tumor effect [10][11]. - The design features a self-reinforcing feedback loop characterized by increased Cu+, enhanced GLS1 inhibitor production, and reduced glutathione (GSH) levels, further promoting the accumulation of Cu+ and enhancing the therapeutic effect [7][11].