Construction and in vitro studies of magnetic-apoferritin nanocages conjugated with KGDS peptide targeted at activated platelets for the MRI diagnosis of thrombus

摘要

Many people have been affected by thrombotic events in several ways, all of which can give rise to the necrosis and death of tissues. Therefore, a sensitive way for detecting thrombus can enhance the efficiency of the diagnosis and the management of thrombosis. This study provided an originally activated platelet-targeted contrast agent for the detection of thrombosis. Utility Gd load apoferritin (Afn) nanocages, for MRI-enhancing contrast, were conjugated with a KGDS peptide, targeting integrin GPIIb-IIIa located on the membrane of human activated platelets. A transmission electron microscope (TEM) and dynamic light scattering (DLS) were used to examine the morphology of the prepared Gd-Afn-KGDS, which had the mean particle size about of 11.59 +/- 0.37 nm with a narrow size distribution (the PDI was 0.21 +/- 0.02). Hemolysis and cytotoxicity studies showed that the prepared Gd-Afn-KGDS had a great affinity for blood cells and vascular endothelial cells. Microscopy and in vitro MR imaging showed that the targeted nanoparticles bind to the blood clot and enhanced thrombus in the T1-weighted imaging, whereas in the control group, the non-targeted nanoparticles did not appear to have the same features. Thus, the evidence shows that the designed thrombus-specific, targeted T1-weighted contrast nanoparticles could potentially provide a benefit in the detection of thrombosis by MRI which could possibly be used in humans and might be useful for accurate thrombus therapy by entrapping thrombolytic drug inside the apoferritin nanocage.