Near-infrared fluorescent protein and bioluminescence-based probes for high-resolution in vivo optical imaging

Abstract

In the last few years, high-resolution near-infrared (NIR) optical imaging has become an indispensable modality for non-invasive visualization of deep tissues both in fundamental life science and preclinical research. This is due to the high tissue permeability, low absorption and low scattering of NIR light as well as the low autofluorescence in the NIR wavelength region (700–1400 nm) in living systems. Compared to magnetic resonance imaging (MRI), X-ray computer tomography (X-ray CT), and positron emission tomography (PET), NIR optical imaging has a high spatiotemporal resolution (∼μm) enough to visualize cellular dynamics at the whole-body level. Additionally, NIR optical imaging does not require high-energy ionizing radiation, such as X-rays, that leads to serious radiation damage of living cells. Furthermore, NIR optical imaging can easily achieve molecular imaging with the aid of NIR optical probes, which specifically bind to biomarkers expressed on cell surfaces. Thus, NIR optical imaging has great potential to be used for non-invasive optical diagnostics of diseases in medical and clinical fields. For such NIR optical imaging, NIR fluorescent probes with high brightness and biocompatibility are crucial. Although a variety of NIR imaging probes based on nanoparticles such as quantum dots and dye-incorporated polymers have been developed, possible applications of these imaging probes to optical contrast agents are limited due to their cytotoxicity. In contrast, fluorescent proteins and bioluminescence-based probes are highly biocompatible and practical for biomedical applications. During the last few years, a variety of NIR optical probes based on engineered proteins have been reported for fluorescence and/or bioluminescence in vivo imaging. This review describes the recent progress on NIR fluorescent proteins and bioluminescence-based probes for high-resolution in vivo optical imaging. The review also covers several cutting-edge optical imaging techniques using NIR fluorescent proteins and bioluminescent probes.