A closed-loop myocardial infarction theranostic platform activated by macrophage-derived nitric oxide and acidic...

Precise management of the inflammatory response after myocardial infarction necessitates targeted engagement of cellular drivers. Here, we report a pathophysiology-guided theranostic platform that exploits two defining features of pro-inflammatory macrophages, their high-output nitric oxide (NO) production and localized acidic microenvironment, to enable concurrent sensing, quantification, and modulation of post-infarction inflammation. The platform, PM720@NRP, is engineered from platelet membranes encapsulating an NO-responsive NIR-II fluorophore and the immunomodulator FTY720. It delivers three integrated functions: (i) specific, NO-activated NIR-II imaging of inflammatory foci; (ii) machine learning-powered translation of imaging signals into quantitative maps of pro-inflammatory macrophage activity; (iii) acid-triggered release of FTY720 to reprogram macrophages toward a reparative phenotype, synergizing with platelet-derived factors to stimulate angiogenesis. This strategy provided real-time visualization and non-invasive quantification of inflammation, while improving cardiac function and repair. By repurposing pathological biomarkers as intrinsic triggers for diagnosis and treatment, this work establishes a closed-loop, biology-inspired paradigm that autonomously adapts to dynamic disease activity.