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.
Organelles play significant roles in mediating communication between and within cells. Furthermore, organelle failure would affect cellular homeostasis and result in a variety of pathophysiologies, such as cancer, metabolic, cardiovascular, and neurodegenerative illness. Since healthy and functional organelles with natural biological functions play important roles in the regulation and recovery of defective cells, exosomes, an extracellular organelle, have been used as viable natural vehicles for drug loading and delivery by using physical and chemical engineering techniques. With the development of synthetic chemistry, materials, and nanotechnology, material-assisted engineering of intracellular organelles has received much research interest. In this Review, we summarize four different strategies for isolated intracellular organelle engineering, including electrostatic interaction, hydrophobic interaction, covalent conjugation, and lipid fusion to highlight how man-made and natural materials could be used to modify organelles and make them more powerful for various applications. We expect this Review could encourage further development in organelle painting techniques, and their compatibility with cell biology would result in novel living materials for efficient theragnostic applications.
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