ROS‐Responsive Nanoplatforms for Atherosclerosis Photoacoustic Diagnosis and Endothelial Cell‐Macrophage Crosstalk Regulation

Abstract As a major causative agent of cardiovascular disease, atherosclerosis (AS) is typically characterized by aberrant lipid buildup and persistent vascular inflammation. However, early AS is difficult to recognize by traditional imaging methods owing to the absence of evident symptoms. Therefore, a reactive oxygen species (ROS)‐responsive theranostic nanoplatform (PA/HFLCD) is developed in order to modulate the endothelial cell‐macrophage crosstalk in a pathological environment and to enable precise detection of early plaques. π‐conjugated polymers (PFDPP‐Se) are synthesized by palladium‐catalyzed arylation polymerization reaction. β‐Cyclodextrin‐modified oxidized dextran is self‐assembled with ferrocene and linoleic acid co‐modified low molecular weight heparin, incorporating PFDPP‐Se as photoacoustic contrast agents. Excessive ROS at the plaque facilitates the breakdown of ferrocene binding to β‐cyclodextrins, releasing both PFDPP‐Se and therapeutic agents to identify lesions by photoacoustic imaging and balancing endothelial cell‐macrophage crosstalk. In vivo studies confirm that PA/HFLCD enables precisely targeted photoacoustic diagnostics and regulates the inflammatory microenvironment consisting of endothelial cells and macrophages in ApoE −/− mice, leading to plaque regression. This synergistic amalgamation of diagnostic and therapeutic attributes renders PA/HFLCD not only a formidable instrument in combating AS, but also a reference for the theranostics of various inflammatory diseases.