Surface hydrolysis-designed AuNPs-zwitterionic-glucose as a novel tool for targeting macrophage visualization and delivery into infarcted hearts.

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Macrophages, innate immune cells, are key players in the maintenance of myocardial homeostasis under normal conditions and tissue repair after injury. The infiltration of macrophages into the injured heart makes them a potentially appealing vehicle for noninvasive imaging and targeted drug delivery of myocardial infarction (MI). In this study, we demonstrated the use of surface hydrolysis-designed AuNPs-zwitterionic-glucose to label macrophages and track their infiltration into isoproterenol hydrochloride (ISO)-induced MI sites noninvasively using CT. The AuNPs-zwitterionic-glucose did not affect the viability or cytokine release of macrophages and were highly taken up by these cells. The in vivo CT images were obtained on Day 4, Day 6, Day 7, and Day 9, and the attenuation was seen to increase in the heart over time compared to the Day 4 scan. In vitro analysis also confirmed the presence of macrophages around injured cardiomyocytes. Additionally, we also addressed the concern of cell tracking or merely AuNP tracking, which is the inherent problem for any form of nanoparticle-labeled cell tracking by using zwitterionic and glucose-functionalized AuNPs. The glucose coated on the surface of AuNPs-zwit-glucose will be hydrolyzed in macrophages, forming only zwitterionic protected AuNPs that cannot be taken up again by endogenous cells in vivo. This will greatly improve the accuracy and precision of imaging and target delivery. We believe this is the first study to noninvasively visualize the infiltration of macrophages into MI hearts using CT, which could be used for imaging and evaluating the possibility of macrophage-mediated delivery in infarcted hearts.