Over-1000 nm near-infrared fluorescent biodegradable polymer nanoparticles for deep tissue in vivo imaging in the second biological window

Near-infrared (NIR) fluorescence bioimaging has received considerable attention in biomedical research owing to its attractive features, such as excellent tissue penetration and low phototoxicity. 1 , 2 Most of the currently used fluorescent probes have several drawbacks, such as low body penetration and high phototoxicity, because they are excited by ultraviolet (UV; <400 nm) or short wavelength visible (VIS; 400–700 nm) light. As an alternative, NIR light solves these problems and provides a new opportunity to observe deep parts of the body with low phototoxicity. Because of this, the NIR wavelength range (700–1800 nm) is called the ‘biological window’ and is widely used for in vivo fluorescence imaging. 3 In particular, the over-1000 nm (OTN-) NIR region is of wide interest as a novel wavelength region for use in fluorescence imaging. The OTN-NIR region consists of the ‘NIR-II’ (the second biological window: 1000–1350 nm) and the ‘NIR-III’ (the third biological window: 1500–1800 nm) regions, and NIR light in these regions can penetrate the body deeper than the currently used NIR-I (first biological window: 700–900 nm) region. 3 , 4 , 5 Various nanomaterials, such as quantum dots, 6 single-wall carbon nanotubes 7 and rare-earth-doped ceramic nanoparticles, 8 , 9 , 10 , 11 are well known to demonstrate OTN-NIR emission; many researchers, including our group, have reported successful in vivo fluorescence imaging using these nanomaterials. However, synthesis of these nanoparticles requires high levels of chemical experimental skill and is time consuming. In addition, these OTN-NIR phosphors comprise metal or inorganic nanomaterials, and thus are difficult to use in human clinical applications.