Different subtypes of breast cancer (BCC) have variable degrees of malignancy, which is closely related to their extracellular pH (pHe). Therefore, it is increasingly significant to monitor the extracellular pH sensitively to further determine the malignancy of different subtypes of BCC. Here, a L-arginine and Eu3+ assembled nanoparticle Eu3+@L-Arg was prepared to detect the pHe of two breast cancer models (TUBO is non-invasive and 4T1 is malignant) using a clinical chemical exchange saturation shift imaging technique. The experiments in vivo showed that Eu3+@L-Arg nanomaterials could respond sensitively to changes of pHe. In 4T1 models, the CEST signal enhanced about 5.42 times after Eu3+@L-Arg nanomaterials were used to detect the pHe. In contrast, few enhancements of the CEST signal were seen in the TUBO models. This significant difference had led to new ideas for identifying subtypes of BCC with different degrees of malignancy.
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.
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