Intercellular aspirin hand-over with dual therapies by liposome-loaded monocytes

Abstract

Abstract Cell-cell communication serves as a foundation concept of intercellular therapeutic hand-over. Despite the commonsense level of understanding, no clear projection has been made to prove the mechanism. Here, the hand-over of aspirin-liposomes from monocytes to inflamed cells is validated under high-resolution time series of 3D imaging in vitro with in vivo confirmation. As a significant value, caveolin is identified to play a major role in mediating the hand-over using cell receptors by super-resolution microscopy, which is induced by the overexpression of caveolin upon inflammation. When aspirin-liposomes are loaded to splenic monocytes, they naturally target inflamed sites efficiently because the spleen is a major site of liposomal clearance from the body in addition to monocyte residence to leave towards inflammatory signals. The delivery efficiency and anti-inflammatory effects of hand-over through intravenous injection are superior to oral injection of soluble aspirin as confirmed in the ischemic hindlimb and fatty liver of mice (targeted therapy). These results are also agreed by the anti-platelet effect in mouse blood over 7 days (prolonged therapy), and the combination of these therapeutic actions effectively rescues atherosclerotic carotid artery of mouse. This study proves the working mechanism of hand-over, suggesting a translational strategy to improve intercellular delivery.