Macrophage-Targeted multifunctional nanoparticles for detection and treatment of intraplaque hemorrhage.

• Breakthrough nanoparticle to distinguish hemorrhagic plaque from other vulnerable plaques via ultrasound, photoacoustic, and magnetic resonance multimodality imaging. • Effective strategy to fill the gap of treatment about intraplaque hemorrhage. • Novel strategy for early diagnosis and visualized treatment of intraplaque hemorrhage. Intraplaque hemorrhage (IPH) is a critical contributor to atherosclerotic plaque progression and destabilization; however, its timely detection and treatment of IPH are limited. In this study, novel macrophage-targeted nanoparticles (NPs) are developed that encapsulate perfluoropentane (PFP) in the core, load MnFe 2 O 4 and ferrostatin-1 (Fer-1) in the polylactic acid-glycolic acid (PLGA) shell, and conjugate CTHRSSVVC peptide on the surface. These NPs exhibit highly sensitive and specific magnetic resonance/photoacoustic/ultrasound multimodal imaging to distinguish the hemorrhagic plaque from other vulnerable plaques accurately. Further, the distribution could be observed in real-time, conducive to individual visualized therapy. The NPs could actively target the M(Hb) cell, which plays a critical role in clearing erythrocyte lysed products within IPH area. Additionally, Fer-1 loaded in the NPs exhibits a controlled release with non-invasive low-intensity focused ultrasound and further rescues the M(Hb) ferroptosis due to overloaded hemoglobin by scavenging lipid peroxides and chelating iron directly, subsequently stabilizing the hemorrhagic plaque without any toxic biological effects. Overall, these intricately designed NPs introduce a safe and effective theranostic strategy for IPH in susceptible populations, which is promising for further clinical applications. [ABSTRACT FROM AUTHOR]