Biomimetic Nanomaterials for the Immunomodulation of the Cardiosplenic Axis Postmyocardial Infarction

Author:

Bose Rajendran JC1,Kessinger Chase W.1,Dhammu Tajinder2,Singh Toolika2ORCID,Shealy Miller W.2ORCID,Ha Khanh1,Collandra Rena1,Himbert Sebastian3,Garcia Fernando J.4,Oleinik Natalia5,Xu Bing1,Vikas 1,Kontaridis Maria I.167,Rheinstädter Maikel C.3,Ogretmen Besim5,Menick Donald R.28,McCarthy Jason R.1ORCID

Affiliation:

1. Department of Biomedical Research and Translational Medicine Masonic Medical Research Institute Utica NY 13501 USA

2. Department of Medicine Division of Cardiology Medical University of South Carolina Charleston SC 29425 USA

3. Department of Physics and Astronomy McMaster University Hamilton ON L8S 4M1 Canada

4. Department of Radiology Stanford University School of Medicine Stanford CA 94305 USA

5. Department of Biochemistry and Molecular Biology and Hollings Cancer Center Medical University of South Carolina Charleston SC 29425 USA

6. Department of Medicine Division of Cardiology Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02115 USA

7. Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School Boston MA 02115 USA

8. Ralph H. Johnson Veterans Affairs Medical Center Charleston SC 29401 USA

Abstract

AbstractThe spleen is an important mediator of both adaptive and innate immunity. As such, attempts to modulate the immune response provided by the spleen may be conducive to improved outcomes for numerous diseases throughout the body. Here, biomimicry is used to rationally design nanomaterials capable of splenic retention and immunomodulation for the treatment of disease in a distant organ, the postinfarct heart. Engineered senescent erythrocyte‐derived nanotheranostic (eSENTs) are generated, demonstrating significant uptake by the immune cells of the spleen including T and B cells, as well as monocytes and macrophages. When loaded with suberoylanilide hydroxamic acid (SAHA), the nanoagents exhibit a potent therapeutic effect, reducing infarct size by 14% at 72 h postmyocardial infarction when given as a single intravenous dose 2 h after injury. These results are supportive of the hypothesis that RBC‐derived biomimicry may provide new approaches for the targeted modulation of the pathological processes involved in myocardial infarction, thus further experiments to decisively confirm the mechanisms of action are currently underway. This novel concept may have far‐reaching applicability for the treatment of a number of both acute and chronic conditions where the immune responses are either stimulated or suppressed by the splenic (auto)immune milieu.

Funder

U.S. Department of Defense

American Heart Association

U.S. Department of Veterans Affairs

National Institute of Arthritis and Musculoskeletal and Skin Diseases

National Heart, Lung, and Blood Institute

Publisher

Wiley

Subject

Mechanical Engineering,Mechanics of Materials,General Materials Science

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