化学动力疗法作为一种新型化疗，能够通过生成反应性氧化物（ROS）加剧氧化应激，破坏DNA结构并诱导细胞凋亡和免疫原性细胞死亡（ICD）。然而，作为肿瘤细胞内在的抗氧化应答，谷胱甘肽（GSH）的表达可以上调，以维持细胞氧化还原平衡并保护肿瘤细胞免受ROS介导的损伤。在这种情况下，同时增加肿瘤细胞中ROS生成和GSH消耗是可行的，然而，在特定亚细胞位点上准确递送和释放GSH清除剂至关重要。因此，我们在此提出了一种GSH响应型介孔有机硅纳米粒子（MON）基础的纳米医药MON-CA-TPP@HA，通过将三苯基膦（TPP）和透明质酸（HA）依次共价地连接到肉桂醛（CA）负载的MON表面，并已经证明这种纳米医药MON-CA-TPP@HA是一种极其有效的治疗乳腺癌的策略，通过诱导乳腺癌细胞的ICD和凋亡来实现。系统的体外实验结果明确表明，该纳米医药可以在HA的帮助下主动靶向肿瘤细胞，随后进入肿瘤细胞，并通过TPP残基精确结合于线粒体上。在肿瘤内过表达的GSH诱导下，MONs中的二硫键断裂，CA分子得以释放，诱导细胞呼吸系统周围的过量ROS，激活氧化应激，诱导乳腺癌细胞的凋亡和ICD。体内实验的结果证实了MON-CA-TPP@HA纳米医药能够有效促进树突状细胞（DC）的成熟和CD 8+ T细胞的活化，并调节M1/M2巨噬细胞的比例，改善肿瘤免疫抑制微环境。因此，我们相信这种纳米医药为未来的癌症治疗开辟了一种新的途径。

Chemodynamic therapy as a novel type of chemotherapy can damage the DNA structures and induce cell apoptosis and immunogenic cell death (ICD) through generating reactive oxygen species (ROS) to aggravate oxidative stress. Nonetheless, as an intrinsic antioxidative response of tumor cells, the expression of glutathione (GSH) can be upregulated to maintain the cellular redox balance and protect the tumor cells from ROS-mediated damage. In this context, it is feasible to simultaneously boost ROS generation and GSH depletion in tumor cells; however, the precise delivery and release of GSH scavengers at specific subcellular sites is of great importance. Herein, we propose a GSH-responsive mesoporous organosilica nanoparticle (MON)-based nanomedicine MON-CA-TPP@HA through sequentially covalently attaching triphenylphosphine (TPP) and electrostatically coating hyaluronic acid (HA) onto the surface of cinnamaldehyde (CA)-loaded MONs, known as MON-CA-TPP@HA, which has been demonstrated to be an extremely effective therapeutic strategy for cancer treatment through inducing ICD and apoptosis of breast cancer cells. Systematic in vitro experimental results clearly revealed that the nanomedicine can actively target the tumor cells with the help of HA, subsequently enter the tumor cells, and precisely bind with the mitochondria through TPP residues. Upon cleavaging the disulfide bond in the MONs triggered by over-expressed GSH within tumors, the CA molecules can be released inducing the excessive ROS in situ surrounding the mitochondria to activate oxidative stress to induce apoptosis and ICD of breast cancer cells. The results of the in vivo experiments confirm that the MON-CA-TPP@HA nanomedicine can effectively promote dendritic cell (DC) maturation and CD 8+ T cell activation and regulate the ratio of M1/M2 macrophages, which improve tumor immunosuppressive microenvironment. It is thus believed that the current nanomedicine has paved a new way for future cancer therapy.