Liver metastasis (LM) occurs in various cancers, and its early and accurate diagnosis is of great importance. However, the detection of small LMs is still a great challenge because of the subtle differences between normal liver tissue and small metastases. Herein, we prepare glutathione (GSH)-responsive hyaluronic acid-coated iron oxide nanoparticles (HIONPs) for highly sensitive diagnosis of LMs through a facile one-pot method. HIONPs greatly enhance the signal of MRI in tumor metastases as T1 contrast agent (CA), whereas they substantially decrease the signal of liver as T2 CA as they aggregate into clusters upon the high GSH in liver. Consequently, MRI contrasted by HIONPs clearly distinguishes metastatic tumors (bright) from surrounding liver tissues (dark). HIONPs with superior LM contrasting capability and facile synthesis are very promising for clinical translation and indicate a new strategy to develop an ultrasensitive MRI CA for LM diagnosis that exploits high GSH level in the liver.
Last. Rita Golfieri(UNIBO: University of Bologna)H-Index: 39
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Computed tomography (CT), magnetic resonance imaging (MRI), and 18-fluorideoxyglucose positron emission tomography (18FDG-PET) are historically the most accurate imaging techniques for diagnosing liver metastases. Recently, the combination of diffusion-weighted imaging and hepatospecific contrast media, such as gadoxetic acid in MRI, have been demonstrated to have the highest diagnostic accuracy, sensitivity, and specificity for detecting liver metastases. Various recent meta-analyses have confi...
Abstract Depletion of glutathione (GSH) is considered a critical pathogenic event promoting alcohol-induced lipotoxicity. We recently show that systemic GSH deficiency in mice harboring a global disruption of the glutamate-cysteine ligase modifier subunit (Gclm) gene confers protection against alcohol-induced steatosis. While several molecular pathways have been linked to the observed hepatic protection, including nuclear factor erythroid 2-related factor 2 and AMP-activated protein kinase pathw...
#1Xingya Jiang(UTD: University of Texas at Dallas)H-Index: 6
#2Bujie Du(UTD: University of Texas at Dallas)H-Index: 10
Last. Jie Zheng(UTD: University of Texas at Dallas)H-Index: 35
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Glutathione-mediated biotransformation in the liver is a well-known detoxification process to eliminate small xenobiotics, but its impacts on nanoparticle retention, targeting and clearance are much less understood than liver macrophage uptake, even though both processes are involved in liver detoxification. By designing a thiol-activatable fluorescent gold nanoprobe that can bind to serum protein and be transported to the liver, we non-invasively imaged the biotransformation kinetics in vivo at...
Abstract Glutathione (GSH), the most abundant cellular non-protein thiol, plays a pivotal role in hepatic defense mechanisms against oxidative damage. Despite a strong association between disrupted GSH homeostasis and liver diseases of various etiologies, it was shown that GSH-deficient glutamate-cysteine ligase modifier subunit (Gclm)-null mice are protected against fatty liver development induced by a variety of dietary and environmental insults. The biochemical mechanisms underpinning this pr...
Iron oxide nanoparticle (IONP)-based magnetic resonance imaging (MRI) contrast agents have been widely used for the diagnosis of hepatic lesions. However, current IONP-based liver-specific MRI contrast agents rely on single-phase contrast enhancement of the normal liver, which is not sensitive enough to detect early stage small hepatocellular carcinomas (HCCs). We herein report i-motif DNA-assisted pH-responsive iron oxide nanocluster assemblies (termed RIAs), which provide an inverse contrast e...
Abstract In the treatment of lung cancer, there is an urgent need of innovative medicines to optimize pharmacological responses of conventional chemotherapeutics while attenuating side effects. Here, we have exploited some relatively unexplored subtle differences in reduction potential, associated with cancer cell microenvironments in addition to the well-known changes in intracellular redox environment. We report the synthesis and application of novel redox-responsive PLGA (poly(lactic-co-glyco...
#1Simon Milette(MUHC: McGill University Health Centre)H-Index: 6
#2Jason K. Sicklick(UCSD: University of California, San Diego)H-Index: 32
Last. Pnina Brodt(MUHC: McGill University Health Centre)H-Index: 41
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Curative treatment for metastatic solid cancers remains elusive. The liver, which is nourished by a rich blood supply from both the arterial and portal venous systems, is the most common site of visceral metastases, particularly from cancers arising in the gastrointestinal tract, with colorectal cancer being the predominant primary site in Western countries. A mounting body of evidence suggests that the liver microenvironment (LME) provides autocrine and paracrine signals originating from both p...
Last. Huanghao Yang(FZU: Fuzhou University)H-Index: 56
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Smart assemblies have attracted increased interest in various areas, especially in developing novel stimuli-responsive theranostics. Herein, commercially available, natural tannic acid (TA) and iron oxide nanoparticles (Fe3O4 NPs) are utilized as models to construct smart magnetic assemblies based on polyphenol-inspired NPs–phenolic self-assembly between NPs and TA. Interestingly, the magnetic assemblies can be specially disassembled by adenosine triphosphate, which shows a stronger affinity to ...
#1Huige Zhou(Center for Excellence in Education)H-Index: 13
#2Jinglong Tang(Center for Excellence in Education)H-Index: 17
Last. Chunying Chen(Center for Excellence in Education)H-Index: 80
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Surface ligands and their densities may significantly influence the optic, electric, and stable properties of inorganic nanoparticles as well as their magnetic resonance imaging (MRI) characters. In this study, ultra-small iron oxide nanoparticles with hyaluronic acid as surface ligand (Fe3O4@HA) were designed to target tumor cells and tune the T1- and T2-weighted MRI by aggregating in the tumor microenvironment via the degradation of HA upon exposure to hyaluronidase (HAase) with decreasing pH....
Functional imaging encompasses techniques capable of assessing physiological parameters of tissues, and offers useful clinical information in addition to that obtained from morphological imaging. Such techniques may include magnetic resonance imaging with diffusion-weighted sequences or hepatobiliary contrast agents, perfusion imaging, or molecular imaging with radiolabelled tracers. The liver is of major importance in oncological practice; not only is hepatocellular carcinoma one of the maligna...