Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, China.
Institute of State Key Laboratory of Targeting Oncology, National Center for International Research of Bio-targeting Theranostics, Guangxi Key Laboratory of Bio-targeting Theranostics, Collaborative Innovation Center for Targeting Tumor Diagnosis and Therapy, Guangxi Medical University, Nanning, Guangxi 530021, China.
Sci Adv. 2024 Nov 8;10(45):eadp7160. doi: 10.1126/sciadv.adp7160.
PANoptosis has recently emerged as a potential approach to improve the immune microenvironment. However, current methods for inducing PANoptosis are limited. Herein, through biological screening, the rational use of the nutrient metal ions Cu and Zn had great potential to induce PANoptosis. Inspired by these findings, we successfully developed hydrazided hyaluronic acid-modified zinc copper oxide (HZCO) nanoparticles as a PANoptosis inducer to potentiate immunotherapy. Bioactive HZCO actively delivered Cu and Zn while disrupting the cellular intrinsic ion metabolism pathway, resulting in double-stranded DNA release and organelle damage in cancer cells. Simultaneously, this process triggered the formation of PANoptosome and the activation of PANoptosis. HZCO-induced PANoptosis inhibited tumor growth and activated potent antitumor immune response, thereby enhancing the effectiveness of anti-programmed cell death 1 therapy. Overall, our work provides an insight into the development of PANoptosis inducers and the design of synergistic immunotherapy strategies.
细胞焦亡作为一种潜在的改善免疫微环境的方法，最近受到关注。然而，目前诱导细胞焦亡的方法有限。在此，通过生物筛选，合理利用营养金属离子 Cu 和 Zn 具有很大的诱导细胞焦亡的潜力。受此启发，我们成功开发了酰腙化透明质酸修饰的锌铜氧化物（HZCO）纳米颗粒作为一种细胞焦亡诱导剂，以增强免疫治疗效果。具有生物活性的 HZCO 主动递送 Cu 和 Zn，同时破坏细胞内固有离子代谢途径，导致癌细胞中的双链 DNA 释放和细胞器损伤。同时，这一过程触发了细胞焦亡小体的形成和细胞焦亡的激活。HZCO 诱导的细胞焦亡抑制了肿瘤生长并激活了有效的抗肿瘤免疫反应，从而增强了抗程序性细胞死亡 1 治疗的效果。总的来说，我们的工作为细胞焦亡诱导剂的开发和协同免疫治疗策略的设计提供了新的思路。
