An Integrative Probe for Tumor Therapy and Dual-Modal Self-Evaluation Imaging of Therapeutic Efficacy

Abstract

Currently, independent tumor therapy and evaluation methods can not achieve real-time evaluation. Therefore, development of a self-evaluation strategy is urgently needed. To the best of our knowledge, there is no multimodal self-evaluation strategy. Herein, we design an integrative probe (CPT-SS-DEVD-HCy) for tumor therapy and dual-modal self-evaluation imaging. In tumor cells, the high concentration of glutathione (GSH) specifically induces CPT-SS-DEVD-HCy to release CPT, which generates apoptosis with the activation of caspase-3 (Casp-3). Subsequently, activated Casp-3 further specifically cleaves peptide substrate to release hemicyanine (HCy) dye, thus generating a fluorescent/photoacoustic (FL/PA) dual-modal signal for self-evaluation imaging. Cell experiments show that CPT-SS-DEVD-HCy can effectively kill tumor cells through GSH-instructed CPT release and further image Casp-3 activity during apoptosis with a 5.1-/6.4-fold increased FL/PA signal. Moreover, CPT-SS-DEVD-HCy displays a high tumor inhibition effect and is competently able to self-evaluate the tumor therapeutic effect in vivo. We envision that this work will be helpful for developing more self-evaluation imaging probes in the future.