Nathan C Ni1, Cheng S Jin2,3, Liyang Cui2,4, Zhengbo Shao1,5, Jun Wu1, Shu-Hong Li1, Richard D Weisel1,6, Gang Zheng7,8,9, Ren-Ke Li10,11,12. 1. Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, Canada. 2. Princess Margaret Cancer Center, University Health Network, Toronto, Canada. 3. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada. 4. Medical Isotope Research Center, Peking University, Beijing, China. 5. Department of Ophthalmology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China. 6. Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, Canada. 7. Princess Margaret Cancer Center, University Health Network, Toronto, Canada. gang.zheng@uhnres.utoronto.ca. 8. Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada. gang.zheng@uhnres.utoronto.ca. 9. MaRS Centre, Toronto Medical Discovery Tower, Room 3-702, 101 College St, Toronto, ON, M5G 1L7, Canada. gang.zheng@uhnres.utoronto.ca. 10. Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, Canada. renkeli@uhnresearch.ca. 11. Department of Surgery, Division of Cardiac Surgery, University of Toronto, Toronto, Canada. renkeli@uhnresearch.ca. 12. MaRS Centre, Toronto Medical Discovery Tower, Room 3-702, 101 College St, Toronto, ON, M5G 1L7, Canada. renkeli@uhnresearch.ca.
Abstract
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.
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.
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