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An Intact Pericardium Ischemic Rodent Model
Published on: September 2, 2021
Non-invasive Macrophage Tracking Using Novel Porphysome Nanoparticles in the Post-myocardial Infarction Murine Heart
Nathan C Ni1, Cheng S Jin2,3, Liyang Cui2,4
1Division of Cardiovascular Surgery, Toronto General Research Institute, University Health Network, Toronto, Canada.
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.
Insights
Researchers developed folate-porphysomes for tracking macrophages after heart attack. This imaging tool revealed dynamic changes in macrophage location and inflammation status in the infarcted heart over 9 days.
Area of Science:
- Biomedical Engineering
- Nanotechnology
- Cardiovascular Research
Background:
- Myocardial infarction (MI) triggers complex inflammatory responses involving macrophages.
- Understanding macrophage behavior post-MI is crucial for developing targeted therapies.
- Current methods for tracking macrophages in the heart have limitations.
Purpose of the Study:
- To develop and validate a novel folate-conjugated porphyrin nanoparticle (porphysome) for multimodal, non-invasive tracking of active macrophages post-myocardial infarction (MI).
- To investigate the dynamic changes in macrophage mobilization, distribution, and phenotype within the infarcted heart over time using the developed porphysomes.
Main Methods:
- Generation of folate-conjugated porphyrin nanoparticles (porphysomes).
- Selective uptake studies of porphysomes by macrophages.
- In vivo tracking of porphysomes in mice post-MI using radioligand and fluorescent imaging.
- Assessment of macrophage phenotype via immunohistochemistry.
Main Results:
- Folate-porphysome uptake by cardiac macrophages was selective.
- Non-invasive imaging successfully detected macrophage mobilization post-MI for up to 9 days.
- Macrophage presence peaked at day 1 and day 7 post-MI, with distinct spatial distributions (ventricle vs. scar).
- Macrophage phenotypes shifted from pro-inflammatory (day 1) to anti-inflammatory within the scar tissue (day 7).
Conclusions:
- Folate-porphysomes are effective for non-invasive imaging and tracking of macrophages in the infarcted heart.
- This technology provides insights into the dynamic behavior and phenotypic changes of active macrophages following myocardial infarction.
- The findings support the use of porphysomes for investigating inflammatory processes in cardiovascular disease.
