免疫疗法在临床上取得了很高的成功，然而，治疗效果在很大程度上受到免疫激活不足和免疫抑制微环境的限制。在此，我们报告了肿瘤微环境（TME）响应性富锰过氧化锌纳米颗粒（MONP），通过诱导癌细胞的免疫原性死亡（ICD）和激活干扰素基因（STING）途径的刺激物，用于协同癌症免疫治疗。 MONP 在暴露于酸性肿瘤组织时尤其会解离，并原位生成·OH 以实现 ICD 效应。此外，Mn2 激活 STING 并协同诱导 I 型干扰素和炎症细胞因子的分泌，以实现特定的 T 细胞反应。同时，MONPs 通过减少 Tregs 并将 M2 巨噬细胞极化为 M1 型来缓解 TME 的免疫抑制，从而释放级联适应性免疫反应。与抗PD-1抗体结合，MONPs在抑制肿瘤生长和预防肺转移方面表现出优异的功效。我们的研究证明了功能性纳米颗粒放大 STING 先天刺激的可行性，展示了癌症免疫治疗的重要策略。

Immunotherapies have shown high clinical success, however, the therapeutical efficacy is largely restrained by insufficient immune activation and an immunosuppressive microenvironment. Herein, we report tumor microenvironment (TME)-responsive manganese-enriched zinc peroxide nanoparticles (MONPs) for synergistic cancer immunotherapy by inducing the immunogenic death (ICD) of cancer cells and activating the stimulator of the interferon gene (STING) pathway. MONPs especially disassociate upon exposure to acidic tumor tissue and in situ generate •OH for the ICD effect. Moreover, Mn2+ activated the STING and synergistically induced the secretion of type I interferon and inflammatory cytokines for specific T cell responses. Meanwhile, MONPs relieved the immunosuppression of TME through decreasing Tregs and polarizing M2 macrophages to the M1 type to unleash a cascade adaptive immune response. In combination with the anti-PD-1 antibody, MONPs showed superior efficacy in inhibiting tumor growth and preventing lung metastasis. Our study demonstrates the feasibility of functional nanoparticles to amplify STING innate stimulation, showing a prominent strategy for cancer immunotherapy.