Non-invasive Macrophage Tracking Using Novel Porphysome Nanoparticles in the Post-myocardial Infarction Murine Heart.

PURPOSE

We generated a folate-conjugated porphyrin nanoparticle (porphysome) suitable for multimodal non-invasive active macrophage tracking post-myocardial infarction (MI).

PROCEDURES

Macrophage uptake of folate-conjugated porphysomes was selective. Folate-porphysome cardiac macrophage tracking was detected in vivo using radioligand and fluorescent imaging. To track post-MI macrophage mobilization, cardiac fluorescence signal in folate-porphysome-injected mice was measured for 9 day post-MI. Active macrophage phenotype was assessed using immunohistochemistry.

RESULTS

Heart active macrophage presence peaked on day 1, returned to baseline by day 3, and peaked again on day 7 post-MI. Macrophages were distributed throughout the left ventricle at day 1, but aggregated within scar tissue at day 7. Macrophage phenotype was pro-inflammatory (TNFα(+)) at day 1, whereas scar-resident macrophages expressed anti-inflammatory markers (IL-10, TGFβ) at day 7. However, day 7 macrophages outside the scar expressed neither pro- nor anti-inflammatory markers.

CONCLUSIONS

We established that folate-porphysomes are suitable for non-invasive imaging of macrophages and used it to investigate active macrophage behavior in the infarcted heart.