Monitoring the Fluctuation of Hydrogen Peroxide in Diabetes and Its Complications with a Novel Near-Infrared Fluorescent Probe

Abstract

Diabetes is one of the metabolic diseases marked by hyperglycemia and is often accompanied by the occurrence of some complications. As a biomarker of oxidative stress, hydrogen peroxide (H 2 O 2 ) has close association with the occurrence and development of diabetes and its complications. Unfortunately, there is no fluorescent probe reported for imaging H 2 O 2 in diabetic mice. Here, a novel near-infrared (NIR) fluorescent probe named QX-B was designed and synthesized to detect H 2 O 2 . For the probe, the quinolinium-xanthene dye is used as the fluorophore and borate ester is chosen as the response group. After the addition of H 2 O 2 , a strong NIR fluorescence signal at 772 nm is observed. The probe not only shows high sensitivity with 10-fold enhancement but also displays excellent selectivity to H 2 O 2 over other possible interfering species. In the meantime, the possible response mechanism of QX-B toward H 2 O 2 was proposed and verified by the high-performance liquid chromatography (HPLC) experiment, mass spectra (MS) experiment, and density functional theory (DFT) calculation. Furthermore, based on the low cell cytotoxicity of QX-B, it has been applied in imaging exogenous and endogenous H 2 O 2 in HeLa cells, HCT116 cells, 4T1 cells, and zebrafish successfully. More importantly, inspired by the performance of NIR fluorescence, QX-B has been used in monitoring H 2 O 2 in diabetic mice for the first time. This provides very important information for the diagnosis and treatment of diabetes and its complications.

Rational design of stable heptamethine cyanines and development of a biomarker-activatable probe for detecting acute lung/kidney injuries via NIR-II fluorescence imaging

“…33,34 Moreover, this was chosen because H 2 O 2 constitutes an important ROS that is involved in various inflammatory diseases where it can serve as an oxidative stress biomarker for such conditions. [35][36][37][38] The introduction of phenylboronic acid into N-methylamine at the para-position of the pyridinium substituent afforded HP-H 2 O 2 . The synthetic route used to access HP-H 2 O 2 is presented in Scheme S2, † and HP-H 2 O 2 's structure was character-ized by high-resolution mass spectrometry, 1 H NMR and 13 C NMR (Fig.…”

Small-molecule fluorescence-based probes for aging diagnosis

“…Mizuta et al have developed two fluorescent probes to detect oxidative stress and the activity of β-gal to evaluate stress-induced premature senescence [38]. The authors first synthesized six candidate fluorescent probes 1a-f for ROS detection and screened the optimal probe 1a (Figure 14A,B [39]. The probe was constructed on the basis of a quinolinium-xanthene fluorophore with long absorption (725 nm) and emission (772 nm) wavelengths.…”

Targeted and activatable nanosystem for fluorescent and optoacoustic imaging of immune-mediated inflammatory diseases and therapy via inhibiting NF-κB/NLRP3 pathways

“…Excessive and uncontrolled inflammation is deleterious and results in a variety of inflammatory diseases. The overexpressed ROS can not only serve as the biomarker for inflammatory diseases, but also the driving force for activating a prodrug for treating various inflammatory diseases, including allergies, autoimmune diseases and metabolic disorders [ [46] , [47] , [48] , [49] , [50] ].…”

“…Moreover, targeted nanodrugs which can give out indicative signals upon activation by ROS would be an ideal theranostic system for in-situ detection of inflammation-related diseases in a non-invasive manner and for on-demand drug release in the disease site, thereby offering accurate diagnosis and precision treatment. Near infrared (NIR) fluorescence imaging technology has been established as a powerful tool for providing a high degree of sensitivity in biomedical applications due to its attractive properties such as high contrast and sensitivity, low cost, absence of ionizing radiation, ease of use, and high specificity [ [50] , [51] , [52] , [53] , [54] , [55] , [56] ]. Recently, to further improve the performance of the optical imaging, such as the elevation of penetration depth and reduction of tissue scattering, the optoacoustic imaging has emerged as a robust and promising modality for live animal imaging [ [57] , [58] , [59] , [60] , [61] , [62] , [63] ].…”