Study On Tumor Hypoxia-Responsive Optical Probes

Hypoxia is a characteristic feature in the microenvironment of most solid tumors. Tumor hypoxia is an important signature of prognosis and also closely related to the chemotherapy and radiotherapy of cancer. The widely-used technique for tumour hypoxia imaging is mainly based on magnetic resonance imaging and positron emission tomography, which still have the problem of high cost and strong background signal and also are hard to allow long-term observation. These problems can be overcome by optical imaging technique. However, due to the lack in the hypoxia-response optical probes, tumor hypoxia imaging using an optical method is still under development.To realize optical imaging of tumor hypoxia, first we need to develop hypoxia-responsive probes with high sensitivity and specificity for further in vivo applications. Despite that many probes have been reported for oxygen sensing in vitro, including phosphorescent transitional metal complexes and small organic molecules containing hypoxia-sensitive chemical groups, research works on the development of probes for in vivo tumour hypoxia imaging are rare. In this paper, we demonstrate the synthesis and application of new macromolecular optical probes. These probes, developed based on iridium (III) complex and biocompatible polymers, are highly sensitive to hypoxia, near-infrared emitting and water-soluble. When applied for in vivo imaging, these probes have the advantage of high biocompatibility, long blood circulation time and effective tumor accumulation and retention. The abilities of these probes in the imaging and measurement of tumor hypoxia have been explored in various animal models. The detailed works are listed below.1) A macromolecular hypoxia-sensitive optical probe has been developed from iridium complex and poly (N-vinylpyrrolidone). Using this probe, the detection of hypoxic tumors in the living mice has been achieved through whole body optical imaging. The quantitative measurement of tumor hypoxia in vivo is also enabled by the probe. The sensitivity of probe is high enough to detect a small amount of cancer cells in vivo before the formation of advanced tumors.2) A micelle-based hypoxia-activated nanosensor has been developed. This nanosensor was applied to track tumor metastasis in vivo. Tumor metastasis to lung or lymph node was detected using this nanosensor through non-invasive whole body optical imaging.3) A two-stage conversion strategy has been proposed for amplifying tumor microenvironment signals. According to this strategy, a new macromolecular probe that successively response to acidity and hypoxia has been designed and synthesized. This probe has been applied to improve tumour to background contrast in the tumor imaging as well as detect small amount of live cancer cells in the mice model.