经典的化学化疗药物可能会引起免疫原性细胞死亡（ICD），随后通过激活CD8+ T细胞促进细胞介导的抗肿瘤免疫反应。然而，由于肿瘤抗原的持续刺激，CD8+ T细胞变得疲惫，这是有效抑制肿瘤生长和转移的主要障碍。在这里，我们开发了一种化疗-基因联合纳米医学方法，以搭建和重新规划化疗和免疫疗法之间的桥梁。双重载药纳米医学通过多柔比星诱导肿瘤细胞的ICD，并通过小干扰RNA逆转疲惫CD8+ T细胞的抗肿瘤效应。具有协同化疗-基因和氟组装的纳米医学富含活性氧物种和酸敏感键，从而导致增强的癌症免疫治疗，抑制乳腺癌和黑色素瘤的肺转移的小鼠模型中肿瘤生长的。该研究为对抗恶性转移性肿瘤的化疗-免疫级联治疗提供了有效的策略和见解。

Classical chemotherapeutic drugs may cause immunogenic cell death (ICD), followed by activating CD8+ T cells to promote cell-mediated antitumor immune responses. However, CD8+ T cells become exhausted due to tumor antigens' continuous stimulation, creating a major obstacle to effectively suppressing tumor growth and metastasis. Here, we develop an approach of chemo-gene combinational nanomedicine to bridge and reprogram chemotherapy and immunotherapy. The dually loaded nanomedicine induces ICD in tumor cells through doxorubicin and reverses the antitumor effects of exhausted CD8+ T cells through the small interfering RNA. The synergistic chemo-gene and fluorine assembly nanomedicine enriched in reactive oxygen species and acid-sensitive bonds results in enhanced cancer immunotherapy to inhibit tumor growth and the lung metastasis of breast cancer in a mouse model of breast cancer and melanoma. This study provides an efficient strategy and insights into chemoimmunological cascade therapy for combating malignant metastatic tumors.