Self-Reporting Ratiometric AIEgen-Peptide Nanoprobes for Activatable Chemotherapy and Noninvasive Imaging of Therapeutic Outcomes
Shicheng Pei, Zhaohan Liu, Qishu Jiao, Qiling Jin, Xuan Luo, Yuanyuan Liu, Shuyao Zhou, Shuqin Pang, Xiaoxing Wu, Keming Xu, Wenying Zhong
Abstract
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.