A novel CEST-contrast nanoagent for differentiating the malignant degree in breast cancer

Different subtypes of breast cancer (BCC) have variable degrees of malignancy, which is closely related to their extracellular pH (pH_e). 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 pH_e 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 pH_e. In 4T1 models, the CEST signal enhanced about 5.42 times after Eu³⁺@l-Arg nanomaterials were used to detect the pH_e. 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.