A Smart Responsive Fluorescence‐MR Nanoprobe for Monitoring Tumor Response to Immunotherapy

Abstract Accurately evaluating tumor responses to immunotherapy is clinically relevant. However, non‐invasive, real‐time visualization techniques to evaluate tumor immunotherapy are still lacking. Herein, a smart responsive fluorescence‐MR dual‐modal nanoprobe, QM(GP)‐MZF(CP), is reported that can be targeted for cleavage by the cytotoxic T cell activation marker granzyme B and the apoptosis‐related marker cysteine‐aspartic acid‐specific protease 3 (Caspase‐3). The probe uses quinoline‐malononitrile (QM), an aggregation‐induced emission luminogen, and Mn‐Zn ferrite magnetic nanoparticles (MZF‐MNPs), a T2‐weighted imaging (T2WI) contrast agent, as imaging molecules that are linked with the substrate peptides specific to granzyme B and Caspase‐3. Therefore, both granzyme B and Caspase‐3 can target and cleave the substrate peptides in QM(GP)‐MZF(CP). Via aggregation‐induced fluorescence imaging of QM and the aggregation‐induced T2WI‐enhanced imaging effect of MZF‐MNPs, the status of T cells after tumor immunotherapy and the subsequent triggering of tumor cell apoptosis can be determined to identify tumor responsiveness to immunotherapy and thereby evaluate the effectiveness of this therapy in the early stages of treatment.