19 F magnetic resonance imaging (MRI) is a powerful non-invasive imaging technique that shows tremendous potential for the diagnosis and monitoring of human diseases. Fluorinated compounds are commonly used as 19 F MRI contrast agents to develop "hot spot" imaging. To achieve high-resolution MR images, a high density of 19 F nuclei are required in the contrast agents. However, due to the inherent hydrophobicity of fluorinated moieties, aggregation of 19 F contrast agents with high fluorine content is often observed in aqueous solution, resulting in attenuated MR signal and low sensitivity, thus significantly limiting their further biological applications. Here we report the synthesis and characterization of a series of polymeric 19 F MRI contrast agents with high fluorine content by copolymerizing the well-known fluorinated monomer 2,2,2-trifluoroethyl acrylate (TFEA) with a highly water soluble monomer 2-(methylsulfinyl)ethyl acrylate (MSEA) using RAFT polymerization. We show that these polymeric contrast agents, although with high fluorine content, display remarkable imaging performance as evidenced by preferable relaxation properties and intense in vitro/vivo MRI signals, demonstrating the huge potential for eventual clinical applications such as MRI-guided disease diagnosis and therapy.
Toll-like receptors (TLRs) are dominant components of the innate immune system. Activated by both pathogen-associated molecular patterns and damage-associated molecular patterns, TLRs underpin the pathology of numerous inflammation related diseases that include not only immune diseases, but also cardiovascular disease (CVD), diabetes, obesity, and cancers. Growing evidence has demonstrated that TLRs are involved in multiple cardiovascular pathophysiologies, such as atherosclerosis and hypertension. Specifically, a trial called the Canakinumab Anti-inflammatory Thrombosis Outcomes Study showed the use of an antibody that neutralizes interleukin-1β, reduces the recurrence of cardiovascular events, demonstrating inflammation as a therapeutic target and also the research value of targeting the TLR system in CVD. In this review, we provide an update of the interplay between TLR signaling, inflammatory mediators, and atherothrombosis, with an aim to identify new therapeutic targets for atherothrombotic CVD.
Overproduction of reactive oxygen species (ROS) is commonly known as a key factor in the progression of many chronic inflammation diseases such as atherosclerosis and rheumatoid arthritis. In this study, a metal oxide nanodot coated-layered double hydroxide (LDH) nanocomposite is constructed for theranostics of ROS-related diseases. This is the first time that both cerium oxide and iron oxide nanoparticles (NPs) were attached on the surface of LDH NPs through electrostatic interaction via the nanoengineering approach. LDHs served as nanocarriers, cerium oxide NPs served as therapeutic agents due to the antioxidant properties, and iron oxide NPs served as magnetic resonance imaging (MRI) contrast agents. In vitro studies have demonstrated that the constructed nanocomposites have good biocompatibility, good antioxidant capacity to reduce ROS level in the cells, as well as satisfying cell imaging effect in MRI. Functionalization of LDH surface with cerium oxide NPs and iron oxide NPs allows the simultaneous therapy and diagnosis of ROS-related diseases, and may also allow biodistribution tracking of the therapeutic cerium oxide NPs.
Cardiovascular disease (CVD) is the leading cause of death worldwide. CVD includes a group of disorders of the heart and blood vessels such as myocardial infarction, ischemic heart, ischemic injury, injured arteries, thrombosis and atherosclerosis. Amongst these, atherosclerosis is the dominant cause of CVD and is an inflammatory disease of the blood vessel wall. Diagnosis and treatment of CVD remain the main challenge due to the complexity of their pathophysiology. To overcome the limitations of current treatment and diagnostic techniques, theranostic nanomaterials have emerged. The term "theranostic nanomaterials" refers to a multifunctional agent with both therapeutic and diagnostic abilities. Theranostic nanoparticles can provide imaging contrast for a diversity of techniques such as magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT). In addition, they can treat CVD using photothermal ablation and/or medication by the drugs in nanoparticles. This review discusses the latest advances in theranostic nanomaterials for the diagnosis and treatment of CVDs according to the order of disease development. MRI, CT, near-infrared spectroscopy (NIR), and fluorescence are the most widely used strategies on theranostics for CVDs detection. Different treatment methods for CVDs based on theranostic nanoparticles have also been discussed. Moreover, current problems of theranostic nanoparticles for CVDs detection and treatment and future research directions are proposed.
The biological applications of cerium oxide nanoparticles (nanoceria) have received extensive attention in recent decades. The coexistence of trivalent cerium and tetravalent cerium on the surface of nanoceria allows the...
The early detection and accurate characterization of life-threatening diseases such as cardiovascular disease and cancer are critical to the design of treatment. Knowing whether or not a thrombus in a blood vessel is new (fresh) or old (constituted) is very important for physicians to decide a treatment protocol. We have designed smart MRI nano-sensors that can detect, sense and report the stage or progression of cardiovascular diseases such as thrombosis. The nanosensors were functionalized with fibrin-binding peptide to specifically target thrombus and were also labelled with fluorescent dye to enable optical imaging. We have demonstrated that our nanosensors were able to switch between the T1 and T2 signal depending on thrombus age or the presence or absence of thrombin at the thrombus site. The developed nanosensors appeared to be non-toxic when tested with Chinese Hamster Ovarian cells within the tested concentrations. The working principle demonstrated in this study can be applied to many other diseases such as cancer.
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