CXCL9+Macrophage-targeted NIR-II aggregation-induced emission nanoprobes for the early diagnosis of myocarditis

The early and accurate detection of myocarditis is of great significance for timely therapeutic intervention and effectively avoiding subsequent fatal cardiovascular events. However, the currently reported methods are not competent for this attempt. Benefit from the excellent properties of optical imaging and nanoscience, a highperformance nano-fluorescent probe was tactfully constructed in this work by taking full advantage of the specific biomarker in the acute myocarditis and an aggregation-induced emission-active molecule with second near-infrared (NIR-II) emission. A systematic study on signature immune cells and relevant targets in the acute phase of myocarditis in both mice and human samples demonstrated that the chemokine of CXCL9 is specifically overexpressed in the inflammatory macrophages. The corresponding anti-CXCL9 sequence peptide was custom synthesized and modified to the periphery of nanoprobe. The efficient and specific targeting of myocarditis in the acute stage by the prepared CXCL9+ macrophages-targeted nanoprobes (TNPs) was confirmed by using the established experimental autoimmune myocarditis (EAM) mice. Moreover, the TNPs exhibited the ability to detect human myocarditis samples in vitro. Noteworthily, the drug treatment efficacy on myocarditis was also accurately evaluated through monitoring the NIR-II fluorescence intensity variation at myocarditis sites, providing a robust tool for anti-myocarditis drug screening. This study is the first investigation of nano fluorescent probes for the acute phase of myocarditis diagnosis and showed great potential for clinical applications.