Cardiovascular disease caused by atherosclerosis remains the main reason of death in the worldwide scale. Although oxidative stress plays a key role in the initiation and progression of atherosclerosis, current antioxidant drugs have limited efficacy. To resolve this problem, we constructed Nox2 siRNA-loaded nanobubbles (PNBs-siNox2) coated with platelet membranes to utilize their antioxidant stress activity and targeting effect for atherosclerosis treatment. After platelet membranes modification, the capacity of PNBs-siNox2 to target collagen, foam cells, or human umbilical vein endothelial cells (HUVECs) was significantly increased. Moreover, our study demonstrated that under ultrasonic irradiation, biomimetic nanobubbles were more effective at targeting atherosclerotic plaques and delivering genes into cells. In the present study, we provided a biomimetic gene loading strategy based on nanoplatform for noninvasive, precise and efficient therapy of atherosclerosis, which further improved the efficiency of gene transfection and effectively slowed the progression of atherosclerotic plaques when combined with ultrasound.Copyright © 2023. Published by Elsevier Inc.