A dual-targeting therapeutic nanobubble for imaging-guided atherosclerosis treatment

Abstract

Atherosclerosis is a cardiovascular disease that seriously endangers human health. Low shear stress (LSS) is recognized as a vital factor in causing chronic inflammatory and further inducing the occurrence and development of atherosclerosis. Targeting imaging and treatment are of substantial significance for the diagnosis and therapy of atherosclerosis. On this ground, a kind of ultrasound (US) imaging-guided therapeutic polymer nanobubbles (NBs) with dual targeting of magnetism and antibody was rationally designed and constructed for the efficiently treating LSS-mediated atherosclerosis. Under the combined targeting effect of an external magnetic field and antibodies, the drug-loaded therapeutic NBs can be effectively accumulated in the inflammatory area caused by LSS. Upon US irradiation, the NBs can be selectively disrupted, leading to the rapid release of the loaded drugs at the targeted site. Notably, the US irradiation generates a cavitation effect that induces repairable micro gaps in nearby cells, thereby enhancing the uptake of released drugs and further improving the therapeutic effect. The prominent US imaging, efficient anti-inflammatory effect and treatment outcome of LSS-mediated atherosclerosis had been verified in vivo on a surgically constructed LSS-atherosclerosis animal model. This work showcased the potential of the designed NBs with multifunctionality for in vivo imaging, dual-targeting, and drug delivery in the treatment of atherosclerosis.