Britton Chance Center for Biomedical Photonics at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, P. R. China.
Key Laboratory of Biomedical Photonics (HUST), Ministry of Education, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, P. R. China.
Nat Commun. 2024 Nov 20;15(1):10060. doi: 10.1038/s41467-024-54469-7.
Cuproptosis is an emerging mode of programmed cell death for tumor suppression but sometimes gets resisted by tumor cells resist under specific mechanisms. Inhibiting copper transporter ATPase (ATP7A) was found to disrupt copper ion homeostasis, thereby enhancing the effect of cuproptosis and eventually inhibiting tumor invasion and metastasis. In this study, we develop a multifunctional nanoplatfrom based on CuS (CAPSH), designed to enhance cuproptosis in tumor cells by specifically targeting ATP7A interference, while combining thermodynamic therapy with immune effects. The release of copper ions from CAPSH and the copper homeostasis interference by siRNA cooperatively increases the concentration of copper ions in tumor cells, which induces effectively cuproptosis and activates immune responses for suppressing development and metastasis of tumor. This nanoplatform simultaneously regulates cuproptosis from both principles of onset and development, facilitating the application of cuproptosis in tumor therapy.
铜死亡是一种新兴的肿瘤抑制程序性细胞死亡方式，但有时会受到肿瘤细胞在特定机制下的抵抗。研究发现，抑制铜转运体 ATP 酶（ATP7A）会破坏铜离子的内稳态，从而增强铜死亡的效果，最终抑制肿瘤的侵袭和转移。在本研究中，我们开发了一种基于 CuS（CAPSH）的多功能纳米平台，旨在通过特异性靶向 ATP7A 干扰来增强肿瘤细胞中的铜死亡，同时结合热力学治疗和免疫效应。CAPSH 释放铜离子和 siRNA 干扰铜内稳态协同增加肿瘤细胞内铜离子的浓度，有效地诱导铜死亡并激活免疫反应，抑制肿瘤的发展和转移。该纳米平台从发病和发展的两个原理上同时调节铜死亡，促进铜死亡在肿瘤治疗中的应用。
