免疫疗法已成为癌症治疗领域中一个有前途的治疗策略。然而，治疗效果受到免疫原性不足和免疫抑制性的肿瘤微环境的影响。本研究开发了一种自增强反应氧化物（ROS）敏感型纳米载体，该载体具有免疫原诱导剂紫杉醇（PTX）和吲哚酶2,3-二氧化物酶1（IDO1）阻断剂1-甲基-D，L-色氨酸（1-MT）的共封装能力，用于肿瘤排斥。该载体由聚（乙二醇）（PEG）作为疏水性区块、酶可降解的1-MT酯和ROS敏感的过草酸酯交联组成。共聚物可自组装成基于前药的纳米颗粒，带有PTX，实现ROS加速PTX释放和PTX诱导ROS生成的正反馈环。我们的纳米颗粒呈现出高效的免疫原性细胞死亡（ICD），刺激抗肿瘤免疫反应，高效的效应T细胞浸润。与此同时，通过IDO抑制，免疫抑制性肿瘤微环境得到调节，通过减少调节性T细胞（Tregs）和M2型肿瘤相关巨噬细胞（M2-TAMs）的浸润。PTX和1-MT的联合应用实现了4T1肿瘤带瘤小鼠的原发性肿瘤退缩和肺转移的减少。因此，上述结果证明了利用ROS放大纳米平台共递送免疫原诱导剂和IDO抑制剂，具有强大的肿瘤化疗免疫治疗潜力。 ©2023.作者（们）。

Immunotherapy has emerged as a promising therapeutic strategy for cancer therapy. However, the therapeutic efficacy has been distracted due to poor immunogenicity and immunosuppressive tumor microenvironment. In this study, a self-augmented reactive oxygen species (ROS) responsive nanocarrier with immunogenic inducer paclitaxel (PTX) and indoleamine 2,3-dixoygenase 1 (IDO1) blocker 1-methyl-D, L-tryptophan (1-MT) co-entrapment was developed for tumor rejection. The carrier was composed of poly (ethylene glycol) (PEG) as hydrophilic segments, enzyme cleavable 1-MT ester and ROS-sensitive peroxalate conjugation as hydrophobic blocks. The copolymer could self-assemble into prodrug-based nanoparticles with PTX, realizing a positive feedback loop of ROS-accelerated PTX release and PTX induced ROS generation. Our nanoparticles presented efficient immunogenic cell death (ICD) which provoked antitumor immune responses with high effector T cells infiltration. Meanwhile immunosuppressive tumor microenvironment was simultaneously modulated with reduced regulatory T cells (Tregs) and M2-tumor associated macrophages (M2-TAMs) infiltration mediated by IDO inhibition. The combination of PTX and 1-MT achieved significant primary tumor regression and reduction of lung metastasis in 4T1 tumor bearing mice. Therefore, the above results demonstrated co-delivery of immunogenic inducer and IDO inhibitor using the ROS amplifying nanoplatform with potent potential for tumor chemoimmunotherapy.© 2023. The Author(s).