PDF(Pubmed)
Abstract：
The induction of cuproptosis, a recently identified form of copper-dependent immunogenic cell death, is a promising approach for antitumor therapy. However, sufficient accumulation of intracellular copper ions (Cu2+) in tumor cells is essential for inducing cuproptosis. Herein, an intelligent cuproptosis-inducing nanosystem is constructed by encapsulating copper oxide (CuO) nanoparticles with the copper ionophore elesclomol (ES). After uptake by tumor cells, ES@CuO is degraded to release Cu2+ and ES to synergistically trigger cuproptosis, thereby significantly inhibiting the tumor growth of murine B16 melanoma cells. Moreover, ES@CuO further promoted cuproptosis-mediated immune responses and reprogrammed the immunosuppressive tumor microenvironment by increasing the number of tumor-infiltrating lymphocytes and secreted inflammatory cytokines. Additionally, combining ES@CuO with programmed cell death-1 (PD-1) immunotherapy substantially increased the antitumor efficacy in murine melanoma. Overall, the findings of this study can lead to the use of a novel strategy for cuproptosis-mediated antitumor therapy, which may enhance the efficacy of immune checkpoint inhibitor therapy.
摘要：
角化的诱导，一种最近确定的铜依赖性免疫原性细胞死亡的形式，是一种有希望的抗肿瘤治疗方法。然而,细胞内铜离子（Cu2）在肿瘤细胞中的充分积累对于诱导角化作用至关重要。在这里，通过用铜离子载体elesclomol（ES）封装氧化铜（CuO）纳米颗粒来构建智能诱导角化的纳米系统。被肿瘤细胞摄取后，ES@CuO降解释放Cu2+和ES协同触发角化,从而显著抑制小鼠B16黑素瘤细胞的肿瘤生长。此外，ES@CuO通过增加肿瘤浸润淋巴细胞和分泌的炎性细胞因子的数量进一步促进角化介导的免疫反应并重新编程免疫抑制肿瘤微环境。此外,ES@CuO与程序性细胞死亡-1（PD-1）免疫疗法的组合显着提高了鼠黑色素瘤的抗肿瘤功效。总的来说,这项研究的结果可以导致使用一种新策略，用于角化介导的抗肿瘤治疗，这可能会增强免疫检查点抑制剂治疗的功效。
