Activatable magnetic resonance nanosensor as a potential imaging agent for detecting and discriminating thrombosis

Abstract

Objective: 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. Non-invasive differentiation between old and fresh thrombi would be of clinical importance to estimate the risk for embolization and the necessity of anticoagulation.

Methods: 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 fluorescence dye to enable optical imaging.

Results: We have demonstrated that our nanosensors were able to switch between T1 and T2 signal depending on thrombus age or the presence or absence of thrombin at the thrombus site. The nano-sensor exhibits T2 effect in the absence of thrombin (dark signal), while it shows T1 effect in the presence of thrombin (bright signal). Since thrombin enzyme is only present in the fresh/new thrombi and absent in the old/aged ones, the nano-sensor is activated by thrombin and shows T1 effect on the fresh thrombi while it is non-activated and shows T2 effect on the old ones.The developed nanosensors appeared to be non-toxic when tested with Chinese Hamster Ovarian cells within the tested concentrations.

Conclusions: Our data shows that these MRI nano-sensors are able to image and distinguish between fresh and old thrombi. This is a “one stop shopping” approach where a single imaging agent can be used to identify and classify thrombus throughout the body. The potential use of these nano-sensors is beyond cardiovascular disease and can also be applied for cancer detection.