Biomimetic Microenvironment Nanomodulators for Reactive Oxygen Species-Responsive T₁-T₂ Dual-Modal Magnetic Resonance Imaging and Visualized Treatment of Atherosclerosis.

Abstract

Atherosclerosis (AS) is a key pathological basis causing major cardiovascular diseases. Its proinflammatory microenvironment, characterized by aggregated inflammatory macrophages, excessive reactive oxygen species, and deficient phagocytosis, plays a pivotal role in driving AS pathogenesis. However, given the complexity of the microenvironment inside atherosclerotic plaques, developing highly effective and comprehensive nanoplatforms for precise diagnosis, efficient therapy, and reliable prognostic evaluation remains a major challenge. Herein, we construct a biomimetic nanomodulator (FeMn/Cur@CM) with responsive T₁-T₂ dual-modal magnetic resonance imaging (MRI) and multifaceted regulation functionalities of the plaque microenvironment for visualized treatment of AS. Coated with a macrophage membrane, curcumin-loaded FeMn/Cur@CM nanoparticles achieve prolonged circulation and specific targeting of inflammatory plaques. Diagnostically, FeMn/Cur@CM functions as a microenvironment-responsive dual-modal MRI contrast agent, amplifying T₁-T₂ signals in plaques. Therapeutically, FeMn/Cur@CM multifacetedly modulates the plaque microenvironment by alleviating oxidative stress, neutralizing protons, promoting macrophage reprogramming, and restoring macrophage efferocytosis. As a result, the integrated theranostic platform demonstrates remarkable plaque regression and simultaneously realizes real-time visualization of lesion progression via dual-modal MRI, providing precise diagnosis of plaque milieu. Through inflammation-targeted intervention coupled with real-time imaging feedback, this biomimetic nanomodulator establishes a promising strategy for the precise treatment of inflammatory vascular diseases, offering translational potential for AS management.