Real-Time Visualization of the Antioxidative Potency of Drugs for the Prevention of Myocardium Ischemia-Reperfusion Injury by a NIR Fluorescent Nanoprobe

Abstract

The burst of the reactive oxygen species (ROS) is the culprit of myocardial ischemia-reperfusion injury. As direct ROS scavengers, antioxidants are clinically documented drugs for the prevention of reperfusion injury. However, some drugs give disappointing therapeutic performance despite their good in vitro effects. Therefore, in vivo assessments are necessary to screen the antioxidants before clinical trials. However, traditional methods such as histological study require invasive and complicated preprocessing of the biological samples, which may fail to reflect the actual level of the unstable ROS with a very short lifetime. Peroxynitrite (ONOO − ) is a characteristic endogenous ROS produced during reperfusion. Here, we modified the ONOO − -responsive near-infrared fluorescent probe on a myocardium-targeting silica cross-linked micelle to prepare a nanoprobe for the real-time monitoring of ONOO − during coronary reperfusion. A ROS-stable cyanine dye was co-labeled as an internal reference to achieve ratiometric sensing. The nanoprobe can passively target the infarcted myocardium and monitor the generation of ONOO − during reperfusion in real-time. The antioxidants, carvedilol, atorvastatin, and resveratrol, were used as model drugs to demonstrate the capability of the nanoprobe to evaluate the antioxidative potency in situ. The drugs were either loaded and delivered by the nanoprobe to compare their in vivo efficacy under similar concentrations or administered intraperitoneally as a free drug to take their pharmacokinetics into account. The imaging results revealed that pharmacokinetics might be the determinant factor that influences the efficacy of the antioxidants.

Fluorescent Probes for Disease Diagnosis

“…In 2022, the Peng group developed the highly sensitive ratiometric fluorescent probe 129 for real-time monitoring of antioxidants in the treatment of cardiac I/R injury ( Figure 58 ). 209 The authors prepared this ONOO – -responsive NIR probe by using xanthene as the fluorophores, its ICT properties being quenched by a masking trifluoromethanesulfonate group. This group can then be removed or cleaved by ONOO – , thus unmasking the ICT and “turning on” the fluorescence at 725 nm.…”

“…(c) The fluorescence ratio FNOF5/FCy3 in the heart could be used to monitor the level of ONOO – in the heart in real time and evaluate the antioxidant capacity of drugs in situ . Reproduced with permission from ref ( 209 ). Copyright 2022 American Chemical Society.…”

Recent Progress of Spectroscopic Probes for Peroxynitrite and Their Potential Medical Diagnostic Applications

“…The triggers of ONOO − -responsive probes with xanthene as a fluorophore core were generally built on (1) oxidation of the hydrazide ( Xan1–Xan15 ) [ 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ], (2) oxidative cleavage of the substituents at the hydroxyl or amino group ( Xan 16–Xan 28 ) [ 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ], (3) oxidation of pyrylium ( Xan 29–Xan 33 ) [ 46 , 47 , 48 , 49 , 50 ], and (4) oxidation of the hydrogenated xanthene ( Xan 34–Xan 37 ) [ 51 , 52 , 53 , 54 ] and others ( Xan 38–Xan 41 ) [ 55 , 56 , 57 , 58 ]. The key elements of the ONOO − response of probes are summarized in Table 1 .…”

Silica Cross-Linked Micelle-Based Theranostic System for the Imaging and Treatment of Acute and Chronic Kidney Injury

“…27 Silica cross-linked micelles (SCLMs) with ultrasmall sizes have long blood circulation half-lives due to the high-density PEG ligands and stealth property toward the reticuloendothelial system. 28 SCLMs have been successfully used as nanocarriers to deliver drugs to tumors, 29−31 heart, 32,33 and biofilms. 34 In the present study, three different sizes of SCLMs were prepared and their targeting ability to the injured kidney were investigated.…”

“…Silica cross-linked micelles (SCLMs) with ultrasmall sizes have long blood circulation half-lives due to the high-density PEG ligands and stealth property toward the reticuloendothelial system . SCLMs have been successfully used as nanocarriers to deliver drugs to tumors, − heart, , and biofilms …”