Self-Reporting Ratiometric AIEgen-Peptide Nanoprobes for Activatable Chemotherapy and Noninvasive Imaging of Therapeutic Outcomes

Efficacious chemotherapy and real-time therapeutic monitoring remain major challenges in cancer treatment. Traditional systems often lack tumor specificity, limiting efficacy, and hindering therapy optimization. Moreover, the absence of real-time monitoring can lead to missed opportunities and increased risks of side effects. Herein, we designed a self-reporting ratiometric AIEgen-peptide nanoprobe (TPE-1­(Hyd-DOX)-DEVD) for activatable chemotherapy and noninvasive imaging of therapeutic outcomes. When doxorubicin (DOX) in the nanoprobe is selectively activated in the acidic tumor microenvironment, the ensuing caspase-3 cascade triggers a morphological transformation of the nanoprobe that amplifies the TPE fluorescence. This enhancement allows the TPE/DOX fluorescence ratio to serve as an indicator for monitoring DOX activation and for providing therapeutic feedback. Both in vitro and in vivo studies demonstrated that TPE-1­(Hyd-DOX)-DEVD exhibited an impressive tumor suppression efficacy and excellent biocompatibility. This study highlights the strong potential of this nanoprobe as a valuable tool for cancer theranostics, offering hope for more effective and personalized treatment strategies.