Mutually reinforced activatable NIR fluorescence/MR bimodal imaging enabled by tumor-specific biomarker amplification

Multimodality imaging has been developed to advance cancer diagnosis. However, developing activatable multimodality imaging probes has faced considerable challenges because of difficulties in the efficient activation of bimodality signals and synergistic integration of the physicochemical properties of each modality. Herein, leveraging probe-induced tumor-specific biomarker amplification, we developed mutually reinforced activatable bimodal probes through the protein nuclear factor erythroid 2-related factor 2 regulation pathway and a Fenton-like reaction for highly efficient and synergistic activatable near-infrared fluorescence (NIRF) and magnetic resonance (MR) bimodal imaging. This paradigm considerably improves bimodal imaging in several models, among which is the broadening of the signal-to-background ratio (approximately 21.5-fold for NIRF and 1.8-fold for MR) in a HepG2 subcutaneous tumor model and permitting precise diagnosis of small tumors (approximately 2 mm) in a metastatic cervical cancer model. This strategy opens inclusive avenues for bimodal imaging, which may further benefit intraoperative imaging in a clinical setting.