Platelet-hitchhike nanomedicine for theranostics of coronary artery dissection via X-CT imaging and inhibiting NLRP3 signaling pathway

Primary or secondary coronary artery dissection can lead to serious cardiovascular diseases such as acute myocardial infarction, arrhythmia, or sudden cardiac death. However, the early identification and timely intervention for coronary artery dissection remain significant clinical gaps. We propose a practical strategy for the theranostics of coronary artery dissection using the stimuli-responsive nanomedicine CIFu. By leveraging the natural process of platelet activation and recruitment to the dissection tissue, CIFu can specifically adhere to activated platelets, thereby achieving platelet-hitchhike targeting to the arterial dissection. Under oxidative stress and the acidic environment in the lesion, CIFu undergoes rapid disassembly, enabling accurate delivery of encapsulated iodinated contrast agent (ICA) and therapeutic drug. Relying on the ICA, CIFu can enhance the visualization of arterial dissection through ex vivo micro-CT imaging, demonstrating proof of concept for its potential future clinical translation to coronary CT angiography. Furthermore, CIFu was found to be associated with the modulation of NLRP3 signaling pathway activity, which correlated with a reduction in the abnormal differentiation of macrophages and smooth muscle cells, thereby further restraining the progression of arterial dissection. By integrating platelet-hitchhike targeting, X-CT imaging, and NLRP3 pathway modulation, CIFu nanomedicine offers an attractive proof-of-concept solution for the theranostics of arterial dissection, with future potential for clinical translation to coronary artery dissection.