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Self-Amplifying pyropCEST Nanoprobes for Pyroptosis-Induced Immunity Imaging in Breast Cancer

Jiali Deng,Yi Zhu,Jingyi Wang,Xinyi Ding,Sunxian Dai,Jiajing Guo,An Chen,Rong Cao,Li Zhang,Haiyu Liu,Xiance Zhao,Xinyang Wu,Hongwei Lu,Zhongling Wang

The accurate non-invasive monitoring of pyroptosis-based immunotherapy is hindered by the lack of sensitive imaging strategies. Here, a self-amplifying chemical exchange saturation transfer (CEST) imaging-guided pyroptosis therapy (pyropCEST) strategy for activating and highly sensitive visualizing pyroptosis-induced immune response is reported. The biocompatible nanoplatform, composed of human serum albumin loaded with gemcitabine, can induce pyroptosis in the tumor microenvironment, promoting dendritic cell maturation and T cell activation. Meanwhile, nanoprobe dissociation enhances chemical exchange between the NH 2 groups within gemcitabine/albumin and bulk water, yielding self-amplified CEST signals and boosting imaging sensitivity to 435% compared to normal physiological conditions. In the subcutaneous tumor mouse model, the long-term accumulation of nanoprobes in the tumor leads to a 2.5-fold increase in CEST signal over free gemcitabine. Changes in CEST signal serve as an indicator for evaluating CD8 + T cell infiltration and tumor growth, exhibiting an excellent “theranostic correlation.” Moreover, integration with multiparametric MRI enables comprehensive tracking of therapeutic outcomes, including suppression of distant metastases. Collectively, this pyropCEST strategy introduces a clinically translatable imaging paradigm for non-invasive, dynamic visualization of pyroptosis and immune microenvironment remodeling.