Myeloperoxidase-Sensitive T₁ and T₂ Switchable MR Imaging for Diagnosis of Nonalcoholic Steatohepatitis

Abstract

Nonalcoholic steatohepatitis (NASH) is the critical stage in the development of nonalcoholic fatty liver disease (NAFLD) from simple and reversible steatosis to irreversible cirrhosis and even hepatocellular carcinoma (HCC). Thus, the diagnosis of NASH is important for preventing the progress of NAFLD into a fatal condition. The oxidative enzyme myeloperoxidase (MPO), which is mostly produced by polymorphonuclear neutrophil granulocytes (NEU), has been identified as a key player in lipid peroxidation in inflamed tissues. Considering that the expression of MPO was much higher in NASH than in the nonalcoholic fatty liver (NAFL) with steatosis, we designed a nanoparticle platform based on ultrasmall iron oxide (USIO) nanoparticles to realize MPO-sensitive NASH diagnosis. After modification of USIO nanoparticles with amphiphilic poly(ethylene glycol) (PEG) and conjugation with 5-hydroxytryptamine (5HT), a physiological substrate for MPO, the final nanocomposite (USIO-DA-PEG-5HT) revealed MPO-mediated aggregation at the inflammatory site of NASH. Meanwhile, the intrinsic T 1 -weighted magnetic resonance (MR) signal of dispersed USIO-DA-PEG-5HT nanoparticles diminishes, while the T 2 -weighted MR signal is amplified owing to the aggregation effect. These USIO-DA-PEG-5HT nanoprobes offer great potential for improving NASH MR imaging diagnostic accuracy and sensitivity compared to existing molecular MR contrast agents with a single imaging modality.

Recent advances in adhesive materials used in the biomedical field: adhesive properties, mechanism, and applications

“…In addition, Yang et al recently reported that a self-expanding, endoscopically deliverable, and viscous hydrogel can be used to prevent gastric perforation. 95 They found that the silicon dioxide coating significantly increased the adhesive strength of the hydrogel in a simulated highly acidic stomach environment. Acid-resistant, tough, and elastic double-network hydrogels were designed using dimethylacrylamide (DMA) and biodegradable cross-linking agents ( N , N ′-cysteamine bis (acrylamide) (CBA) and sodium alginate (SA)) used to crosslink calcium ions.…”

“…32,94 Therefore, after modifying some of their functional sites using chemical or bioengineering methods, an increasing number of composite adhesive materials have been prepared, including composites formed between viscous biomolecules, composites between biomolecules, and chemical modification. 95 There are many methods used to prepare composite adhesive materials, which can be roughly divided into physical mixing, modular gene, and chemical grafting methods. 22…”

Integrin-Targeted Theranostic Nanoparticles for Clinical MRI-Traceable Treatment of Liver Fibrosis

“…Among a wide variety of CAs, iron oxide nanoparticles (IONPs) have been developed as promising MRI CAs, which can provide high-sensitivity contrast due to their potent superparamagnetic properties . Recently, several sensitive and targeted IONPs have been developed for MR detection and grading of liver diseases using a 7 or 9.4 T MR system. , However, the increase of magnetic field strength significantly improves the resolution but also elevates the cost and price, reducing the clinical feasibility. Therefore, novel CAs should be developed to overcome the shortcomings of low tissue resolution caused by low magnetic field strength on the clinical 3 T MR system.…”

Imaging Fibrosis Progression in NASH with an Allysine-Reactive AIE Probe

“…It can react with the aldehyde group on allylsine, the product of LOX, to turn on its fluorescence. Subsequently, we applied TPAH to monitor fibrosis along with NASH progression using methionine- and choline-deficient (MCD) diet-fed mice as the model. - Early-stage fibrosis was observed in MCD diet-fed mice from 8 weeks onward. Notably, the administration of an LOX inhibitor for two weeks significantly reduced the fibrosis, as evident by Picrosirius Red staining and in vivo fluorescence signal after TPAH injection, suggesting the role of LOX activity in fibrosis progression.…”