Renal Clearable New NIR Probe: Precise Quantification of Albumin in Biofluids and Fatty Liver Disease State Identification through Tissue Specific High Contrast Imaging in Vivo

Abstract

Development of a highly photostable, renal clearable, and nontoxic new NIR probe (CyG) for precise quantification of albumin in different biofluids and liver targeted in vivo albumin visualization is demonstrated. CyG's inherent property to interact selectively with albumin among different biomolecules in intracellular environment with high degree of sensitivity helps CyG in targeted liver imaging. In addition to its long excitation/emission wavelengths (λ = 740 nm, λ = 804 nm), which are much above the biological tissue opaque window (400-700 nm) ensuring better photon penetration, diminished tissue autofluorescence and high contrasts, its molecular mass and size are far below the renal cutoff and hence, CyG qualifies as imaging material for clinical studies. We anticipate that CyG will provide new strategies to overcome the pitfall of present day albumin detection methods as well as accelerate the detection process at relatively lower costs without compromising the accuracy of detection. Moreover, the renal excretion kinetic and intrahepatic albumin binding affinity of CyG can further be used to differentiate between fatty liver from healthy liver in an experimentally arrived mouse model using noninvasive technique.

Simultaneous Detection of Human Serum Albumin and Sulfur Dioxide in Living Cells Based on a Catalyzed Michael Addition Reaction

“…Nowadays, fluorescence detection has attracted considerable attention in monitoring bioactive species with high-contrast spatiotemporal resolution in a noninvasive manner. Among the developed fluorescent tools, several outstanding fluorescent small-molecule probes for the detection and visualization of HSA and SO 2 individually have been developed. − However, these fluorescent probes only focus on the selective detection of a single analyte, and none of them can simultaneously respond to both HSA and SO 2 , despite the two species interacting in many related biological issues. A possible solution is the combination of multiple probes; however, the cross-talk, differing localization, distinct metabolism, and high toxicity of these probes can complicate this approach .…”

Advances in Optical Imaging of Nonalcoholic Fatty Liver Disease

“…[49] Probe 17 displayed a 130-fold enhancement of ratiometric fluorescence (F 469nm /F 703nm ) for tracking ONOO À with high specificity and sensitivity. Leveraging [39] Copyright © 2017, American Chemical Society. (D) The structure and reaction mechanism of probe 15.…”

“…Albumin plays an important role in the transportation of numerous endogenous and exogenous molecules, such as drugs, fatty acids, and lipid metabolites in the circulatory system [38] . And it has been found that the levels of albumin are closely related to a variety of human liver diseases such as chronic hepatitis and cirrhosis [39] . In 2017, Ghosh et al .…”

“…However, the reduction of intrahepatic albumin levels in NAFLD will lead to faster metabolism of probe 13 in a fatty liver model and a reduced in vivo retention time. Compared with healthy livers, the fluorescence intensity of livers was significantly decreased (Figure 10C) in NAFLD mice, which can be used to differentiate the mice with fatty livers from the normal livers of mice by intravital imaging [39] …”

Molecular Scale Optimum Hydrophobicity To Establish an Enhanced Probe–Protein Interaction: Near-Infrared Imaging of Albumin Biosynthesis Modulation

“…In this regard, small organic molecular probes specific to albumin having excitation (>730 nm) and emission (∼800 nm) in the NIR-I window were developed not only to understand the effect of hyperinsulinemia on albumin synthesis but also to establish the role of hydrophobicity to exert an effective interaction with the biomolecules, resulting in a strong optical signal as well as images with good contrast. Probing molecules in the NIR window (700–1700 nm) have their inherent advantages of minimized tissue autofluorescence, deep tissue imaging capability, and reduced photon scattering. − Moreover, during the last two decades, given the importance of this most abundant protein, quite a number of efficient fluorescent probes have been developed for albumin detection and quantification in biofluids. − In addition, fluorescence imaging using an NIR probe has been explored successfully to investigate various bioevents associated with albumin concentration . Thus, emerging toward the microscopic era and appreciating the importance of fluorescence imaging in various biological applications, attempts here have been directed toward studying the effect of chronic hyperinsulinemia on albumin homeostasis.…”