Magnetic Hollow Mesoporous Organosilica Nanocapsule-loaded Platelet For Targeted Magnetic Resonance Imaging Of Artery Thrombosis

The mortality rate of cardiovascular disease has exceeded the tumor,and become the most cause of death throughout the world.However,arterial thrombosis is the pathological basis of stroke,myocardial infarction and other high morbidity and mortality cardiovascular disease.Besides,early diagnosis of thrombosis is still a major clinical challenge.Therefore,it’s important to study the imaging of arterial thrombosis which conforms the clinical symptom.This work which based on the need for accurate molecular imaging of thrombus,focus on the biocompatibility of the hollow mesoporous silica（HMSNs）,the targeted adhesion to the thrombus for platelets,and the magnetic resonance imaging（MRI）.The systematic work has been carried out,which are summarized as follows:（1）Synthesis of hollow mesoporous organosilica nanocapsule encapsulating superparamagnetic iron oxides inside（denoted as OSNCs）The unique characteristics of mesoporous silica nanoparticles（MSNs）,including large surface area,high pore volume,tunable pore size,high biocompatibility,make them promising candidates as nanocarriers to deliver dugs and become the most clinical value nanocarriers.First,Synthesis of Fe3O4 nanoparticles（Fe3O4 NPs）,and then synthesis hollow mesoporous organosilica nanocapsules（OSNCs）encapsulating Fe3O4 NPs by one-step emulsification.The results show that obtained PeA@OSNC has a hollow structure and with mean diameter of about 82 nm,and numerous Fe3O4 are uniformly distributed as satellites surrounding the hollow sphere.The T2 relaxivity coefficient（r2）value of OSNC is measured to be 303.5 mM^-1·s^-1 which indicated that OSNCs has excellent magnetic properties.（2）Platelets labeled with OSNCs（OSNCs@PLT）Considering the biocompatibility and limitations of targeting ability for OSNCs,in this work,the platelets were used as the guider and targeted the thrombus.due to the instinct to vascular injuries and target thrombosis,thus,platelets can deliver the OSNCs to the sites of thrombus.The results of TEM images and Prussian blue staining showed that platelets could be labeled with OSNCs successfully,and the labeling rates reached 12 fg·platelet^-1 when the concentration of Fe in OSNCs increased to 100 μg·mL^-1.According to the cytotoxicity test of bEnd.3 cells,the cell viability of OSNCs@PLT（99%）was higher than OSNCs（86%）,which indicated that Platelet could reduce the toxic effects of ONSCs.Meanwhile,the relaxation rate of OSNCs@PLT was measured as 337.4 mM^-1·s^-1,which indicated that platelets didn’t affect the relaxation rate of OSNCs.The aggregation test of platelets showed that the aggregation ability of platelets labeled with OSNCs was similar with pure Platelets,indicating that the activity of platelets didn’t change due to the presence of OSNCs.Regulating the concentration and period of FeCl₃,thrombosis which is similar to the human clinical spontaneous can be designed as non-occlusive thrombus,which is conducive to circulation of contrast and angiography.The ultrasound imaging and frozen section staining show that non-occlusive thrombus was formed by 10% FeCl₃ within 5 min.Magnetic resonance imaging（MRI）is widely used in imaging study of various diseases because of its high spatial resolution and noninvasive treatment.After the established of thrombosis model,the rats were transplanted into a MR imaging system.The results showed that OSNCs@PLT has obvious targeting and imaging effects than OSNCs and pure platelets.