NIRII‐HDs: A Versatile Platform for Developing Activatable NIR‐II Fluorogenic Probes for Reliable In Vivo Analyte Sensing

Abstract

Small‐molecule‐based second near‐infrared (NIR‐II) activatable fluorescent probes can potentially provide a high target‐to‐background ratio and deep tissue penetration. However, most of the reported NIR‐II activatable small‐molecule probes exhibit poor versatility owing to the lack of a general and stable optically tunable group. In this study, we designed NIRII‐HDs, a novel dye scaffold optimized for NIR‐II probe development. In particular, dye NIRII‐HD5 showed the best optical properties such as proper pKa value, excellent stability, and high NIR‐II brightness, which can be beneficial for in vivo imaging with high contrast. To demonstrate the applicability of the NIRII‐HD5 dye, we designed three target‐activatable NIR‐II probes for ROS, thiols, and enzymes. Using these novel probes, we not only realized reliable NIR‐II imaging of different diseases in mouse models but also evaluated the redox potential of liver tissue during a liver injury in vivo with high fidelity.

Hyperbranched Polymer Dots with Strong Absorption and High Fluorescence Quantum Yield for In Vivo NIR-II Imaging

“…Driven by the clinical needs, a wide range of in vivo probes have been explored, including nanoparticles, − small-molecule dyes, − etc. Among these materials, semiconducting polymer dots (Pdots) have been demonstrated as a class of promising fluorescent probes due to their excellent photostability, high single-particle brightness, good biocompatibility, etc. − Though Pdots with NIR-II emission have been reported, − their optical properties, including the absorption cross-section and the fluorescence quantum yield (QY), still require further optimization.…”

Aminopeptidase N Activatable Nanoprobe for Tracking Lymphatic Metastasis and Guiding Tumor Resection Surgery via Optoacoustic/NIR-II Fluorescence Dual-Mode Imaging

“…Based on its unique features, there have been attempts to employ the NIR-II fluorescence imaging method to guide the resection of tumors in lymph nodes during surgery. , However, most of these NIR-II fluorescent contrast agents or probes used for imaging-guided tumor resection surgery are nonactivatable probes that emit always-on fluorescent signals regardless of whether they interact with the disease biomarkers and consequently constitute noticeable background noise signals. On the contrary, a biomarker-activatable probe gives out NIR-II fluorescent signals only when it is activated by the specific disease biomarker. − As biomarker-activatable probes are capable of responding to specific disease biomarkers and thus emitting varying signals for disease diagnosis and determination of disease site, − integrating a biomarker-activatable probe with NIR-II fluorescence imaging and MSOT imaging would render a robust and utilitarian tool for tracking and monitoring lymphatic metastasis as well as guiding tumor resection.…”

NIR-II Dyad-Doped Ratiometric Nanosensor with Enhanced Spectral Fidelity in Biological Media for In Vivo Biosensing

“…Owing to the ease of multiple-function integration, such as surface functionalization, targeting ability, enhanced water solubility, and improved sensing signal, ratiometric nanosensors have been widely used in biological detection. ,, However, there have been rising concerns on the quantitative reliability of ratiometric sensing for in vivo study. ,, Ratiometric sensors with a short emission wavelength (<700 nm) are susceptible to light scattering and autofluorescence interference in tissue, which superimpose on spectra to compromise sensing accuracy (Scheme ). Owing to the inverse wavelength of dependence of both Mie and Rayleigh scattering, as well as reduced autofluorescence at progressively long wavelength, fluorescent sensors with emission at the second near-infrared window (NIR-II, 1000–1700 nm) allow for biosensing in deep tissues. ,,− A few recent studies have highlighted the wavelength-dependent signal bias in scattering media ,, and accordingly provided several optical approaches for improved reliability of ratiometric sensing in vivo, such as spectral ratioing based on similar light–matter interaction or frequency filtering . Despite these previous studies, limited attention has been given to the spectra shift and distortion of ratiometric sensors in a complex environment (Scheme ).…”