Successively activatable ultrasensitive probe for imaging tumour acidity and hypoxia

Molecular imaging probes for biomarker-based diagnosis typically target, with limited sensitivity, a single molecular process or event in a complex biological system. Here, we show that the macromolecular near-infrared poly(ethylene glycol)-conjugated iridium (iii) complex can be designed to successively respond to tumour acidity and hypoxia while amplifying detection sensitivity via signal propagation. We used the probe to detect, by near-infrared imaging, primary tumours and metastatic tumour nodules as small as 1 mm in mice, and to measure the in vivo metabolic rate of cancer cells. We anticipate that probes for imaging coupled biological events with amplified detection sensitivity will offer opportunities for enhanced molecular diagnostics and image-guided biomedical applications.