Nanoimmunotherapy to treat ischaemic heart disease

Item does not contain fulltextAtherosclerosis is a chronic disease of the large arteries and the underlying cause of myocardial infarction and stroke. Atherosclerosis is driven by cholesterol accumulation and subsequent inflammation in the vessel wall. Despite the clinical successes of lipid-lowering treatments, atherosclerosis remains one of the major threats to human health worldwide. Over the past 20 years, insights into cardiovascular immunopathology have provided a plethora of new potential therapeutic targets to reduce the risk of atherosclerosis and have shifted the therapeutic focus from lipids to inflammation. In 2017, the CANTOS trial demonstrated for the first time the beneficial effects of targeting inflammation to treat cardiovascular disease by showing that IL-1beta inhibition can reduce the recurrence rate of cardiovascular events in a large cohort of patients. At the same time, preclinical studies have highlighted nanotechnology approaches that facilitate the specific targeting of innate immune cells, which could potentially generate more effective immunomodulatory treatments to induce disease regression and prevent the recurrence of cardiovascular events. The clinical translation of such nanoimmunotherapies and their application to treat patients with ischaemic heart disease are challenges that lie ahead

Targeting Trained Innate Immunity With Nanobiologics to Treat Cardiovascular Disease

[Figure: see text]

In vivo imaging of cerebral glucose metabolism informs on subacute to chronic post-stroke tissue status - A pilot study combining PET and deuterium metabolic imaging.

Recanalization therapy after acute ischemic stroke enables restoration of cerebral perfusion. However, a significant subset of patients has poor outcome, which may be caused by disruption of cerebral energy metabolism. To assess changes in glucose metabolism subacutely and chronically after recanalization, we applied two complementary imaging techniques, fluorodeoxyglucose (FDG) positron emission tomography (PET) and deuterium ((2)H) metabolic imaging (DMI), after 60-minute transient middle cerebral artery occlusion (tMCAO) in C57BL/6 mice. Glucose uptake, measured with FDG PET, was reduced at 48 hours after tMCAO and returned to baseline value after 11 days. DMI revealed effective glucose supply as well as elevated lactate production and reduced glutamate/glutamine synthesis in the lesion area at 48 hours post-tMCAO, of which the extent was dependent on stroke severity. A further decrease in oxidative metabolism was evident after 11 days. Immunohistochemistry revealed significant glial activation in and around the lesion, which may play a role in the observed metabolic profiles. Our findings indicate that imaging (altered) active glucose metabolism in and around reperfused stroke lesions can provide substantial information on (secondary) pathophysiological changes in post-ischemic brain tissue

Imaging-assisted nanoimmunotherapy for atherosclerosis in multiple species

Item does not contain fulltextNanomedicine research produces hundreds of studies every year, yet very few formulations have been approved for clinical use. This is due in part to a reliance on murine studies, which have limited value in accurately predicting translational efficacy in larger animal models and humans. Here, we report the scale-up of a nanoimmunotherapy from mouse to large rabbit and porcine atherosclerosis models, with an emphasis on the solutions we implemented to overcome production and evaluation challenges. Specifically, we integrated translational imaging readouts within our workflow to both analyze the nanoimmunotherapeutic's in vivo behavior and assess treatment response in larger animals. We observed our nanoimmunotherapeutic's anti-inflammatory efficacy in mice, as well as rabbits and pigs. Nanoimmunotherapy-mediated reduction of inflammation in the large animal models halted plaque progression, supporting the approach's translatability and potential to acutely treat atherosclerosis