Functionalized Nanovesicles For Atherosclerotic Plaque Theranostics

Acute cardiovascular and cerebrovascular diseases have become the leading cause of death worldwide,and the main pathological basis is atherosclerosis.At present,research is focused on the use of Bio-nanomaterials as a carrier for the diagnosis and treatment of atherosclerotic plaques.Cell-derived extracellular vesicles have higher biocompatibility and longer cycle times than chemically synthesized materials.In addition,genetic engineering technology can be used to modify the specific membrane protein of the cell membrane to mediate the specific binding of the extracellular vesicle vector to the target cell.It provides a new tool for the integration of diagnosis and treatment for atherosclerotic plaque at the molecular and cellular levels.In this study,genetically engineered technology was used to express the plaque-specific polypeptide LyP-1 on the cell membrane.Nano-vesicles(LNVs)were prepared by gradient centrifugation and characterized by DLS,TEM and Zeta potentials.The targeting of plaque macrophages and foam cells was detected by laser confocal microscopy and flow cytometry using Dil-labeled nanovesicles.The MINPs were loaded with LNVs as a carrier and characterized by fluorescence,photoacoustic and magnetic resonance properties.Construction of atherosclerotic model ApoE-/-mice,inj ection of LNV@MINPs in the tail vein,Fluorescence,photoacoustic and magnetic resonance multimodal imaging of carotid plaque in ApoE-/-mice,and quantitative analysis of its effect on carotid plaque enrichment.The 808nm laser was used to irradiate the carotid plaque for photothermal therapy under imaging guidance.In the course of treatment,color Doppler ultrasound was used to monitor the vascular resistance index RI value to assist evaluation,and finally the aortic oil red O staining was used to judge the therapeutic effect.The results showed that the target polypeptide LyP-1 was successfully expressed on the cell membrane,and LNVs with uniform size and good stability were prepared by extracting cell membrane,It has good targeting to plaque macrophages and foam cells.Fluorescence and photoacoustic imaging of carotid plaques in ApoE-/-mice at different time points showed that the enrichment effect of LNV@MINPs in the plaque was significantly stronger than control groups,and reached the enrichment peak at 12h.Magnetic resonance imaging showed that the ratio of Ti signal intensity after LNV@MINPs injection was significantly higher than before injection.During 808nm laser irradiation of carotid plaque,the RI value of LNV@MINPs after 12h + laser irradiation(808nm,0.75W/cm2,3min)decreased significantly,and oil red O staining showed a decrease in aortic plaque area.In summary,we have successfully prepared functionalized nanovesicles that specifically target plaques.We achieved fluorescence,photoacoustic,and magnetic resonance multimodal imaging of carotid plaques in atherosclerotic model ApoE-/-mice.As well as photothermal therapy under imaging guidance,non-invasive monitoring of therapeutic effects is achieved by color Doppler ultrasound during the treatment.Great integration potential for the integration of theranostics in the early stages of atherosclerosis.