State Key Laboratory of Organic-Inorganic Composites, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.
Adv Mater. 2024 Aug;36(35):e2404971. doi: 10.1002/adma.202404971. Epub 2024 Jul 4.
Cuproptosis is a novel copper-dependent programmed cell death. The efficacy of cuproptosis is highly dependent on intracellular copper accumulation and counteracted by a high level of glutathione (GSH) in tumor cells. Here, this work develops a self-amplified cuproptosis nanoparticles (Cel-Cu NP) using celastrol (Cel), a natural product isolated from medical plant. In Cel-Cu NP, Cel serves as a versatile copper ionophore, exhibiting an ideal coordination capacity toward copper ions without compromising the cuproptosis induction. Notably, Cel can simultaneously scavenge GSH content to amplify cuproptosis. Moreover, this self-amplified cuproptosis further activates immunogenic cell death (ICD) to elicit robust immune response. Combining with immune checkpoint blockade, Cel-Cu NP effectively eradicates metastatic tumors in a mouse lung metastasis model. This study provides an efficient nanomedicine by inducing self-amplified cuproptosis for robust immunotherapy.
铜死亡是一种新型的铜依赖性程序性细胞死亡。铜死亡的疗效高度依赖于细胞内铜的积累，并被肿瘤细胞中高水平的谷胱甘肽 (GSH) 所拮抗。在这里，本工作使用来源于药用植物的天然产物雷公藤红素 (Cel) 开发了一种自扩增的铜死亡纳米颗粒 (Cel-Cu NP)。在 Cel-Cu NP 中，Cel 作为一种多功能铜离子载体，对铜离子表现出理想的配位能力，而不会损害铜死亡的诱导。值得注意的是，Cel 可以同时清除 GSH 含量以放大铜死亡。此外，这种自扩增的铜死亡进一步激活免疫原性细胞死亡 (ICD) 以引发强烈的免疫反应。结合免疫检查点阻断，Cel-Cu NP 有效地在小鼠肺转移模型中消除了转移性肿瘤。本研究通过诱导自扩增的铜死亡为强大的免疫治疗提供了一种有效的纳米医学。
