Oxidative stress biomarker triggered multiplexed tool for auxiliary diagnosis of atherosclerosis

Abstract

Oxidative stress is integral in the development of atherosclerosis, but knowledge of how oxidative stress affects atherosclerosis remains insufficient. Here, we design a multiplexed diagnostic tool that includes two functions (photoacoustic imaging and urinalysis), for assessing intraplaque and urinary malondialdehyde (MDA), a well-recognized end-product of oxidative stress. Molecular design is conducted to develop the first near-infrared MDA-responsive molecule (MRM). Acid-unlocked ratiometric photoacoustic nanoprobe is designed to report intraplaque MDA, enabling it to reflect plaque burden. Furthermore, MRM is tailored for urinary MDA detection with excellent specificity in a blind study. Moreover, we found a significant difference in urinary MDA between healthy adults and atherosclerotic patients (more than 600 participants). Combining these two functions, such a multiplexed diagnostic tool can dynamically report intraplaque and systemic oxidative stress levels during atherosclerosis progression, pneumonia infection, and drug treatment in atherosclerotic mice, which is promising for the auxiliary diagnosis of atherosclerosis.

In Vivo Imaging of γ-Glutamyl Transferase in Cardiovascular Diseases with a Photoacoustic Probe

“…From the aorta, 1–5 cross sections were extracted for PA imaging to minimize the errors caused by the placement of mice in the experiment. According to previous reports, , although blood affected the PA signal of the probe, it did not impact the trend of signal changes during the response toward GGT. Then, both the control and AS groups were intravenously injected with HDS-GGT (1 mg/kg), and the PA images of each group were recorded at 720 nm at different time points of 5 min, 12 h, and 24 h (Figure b).…”

“…Therefore, the basic safety of HDS-GGT was guaranteed for in vivo imaging. In particular, since the mice were anesthetized only during imaging, according to the protocol of a previous report, the scanning positions of the mice were basically kept consistent, and the entire abdominal aortic region (the boxed area in Figure S11) was scanned. From the aorta, 1–5 cross sections were extracted for PA imaging to minimize the errors caused by the placement of mice in the experiment.…”

Site-Specific Cascade-Activatable Fluorogenic Nanomicelles Enable Precision and Accuracy Imaging of Pulmonary Metastatic Tumor

“…The development of site-specific activation fluorogenic probes has significantly enhanced the sensitive identification of tumors, enabling precise detection and localization of tumor metastases with a high signal-to-background ratio (SBR). − However, most activatable fluorogenic probes are limited to a single stimulus, rendering them vulnerable to physiological and pathological fluctuations and compromising their accuracy in distinguishing underdiagnosed lung metastases. To overcome this limitation, multistimuli-activatable fluorogenic probes have been proposed, which can intelligently respond to multiple specific indicators to produce a low-background and specific imaging signal compared to single-stimulus probes. − …”

Helper Lipid-Enhanced mRNA Delivery for Treating Metabolic Dysfunction-Associated Fatty Liver Disease

“…In addition, there was a dose-dependent reduction in liver triglycerides following intravenous injection of LNP mCCTα (Figure E). Moreover, the liver malondialdehyde content, a crucial indicator of oxidative stress, exhibited a significant reduction after LNP mCCTα treatment (Figure F). The 0.375 mg kg –1 dose led to a substantial 46.04% reduction in serum free fatty acid levels (Figure S22A) and a substantial 34.80% reduction in serum low-density lipoprotein cholesterol (Figure S22B), a biomarker associated with heart diseases like atherosclerosis .…”