Journal
ADVANCED FUNCTIONAL MATERIALS
Volume 29, Issue 4, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/adfm.201803567
Keywords
biomimetics; drug delivery; ischemic injury; platelets; stromal cell secretome
Categories
Funding
- National Institutes of Health [R01 HL123920, HL137093]
- American Heart Association [18TPA34230092]
- North Carolina State University Chancellor's Innovation Fund
- UNC General Assembly Research Opportunities Initiative award
- State of North Carolina
- National Science Foundation [ECCS-1542015]
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Cardiovascular disease is the leading cause of mortality worldwide. While reperfusion therapy is vital for patient survival post-heart attack, it also causes further tissue injury, known as myocardial ischemia/reperfusion (I/R) injury in clinical practice. Exploring ways to attenuate I/R injury is of clinical interest for improving post-ischemic recovery. A platelet-inspired nanocell (PINC) that incorporates both prostaglandin E2 (PGE(2))-modified platelet membrane and cardiac stromal cell-secreted factors to target the heart after I/R injury is introduced. By taking advantage of the natural infarct-homing ability of platelet membrane and the overexpression of PGE(2) receptors (EPs) in the pathological cardiac microenvironment after I/R injury, the PINCs can achieve targeted delivery of therapeutic payload to the injured heart. Furthermore, a synergistic treatment efficacy can be achieved by PINC, which combines the paracrine mechanism of cell therapy with the PGE(2)/EP receptor signaling that is involved in the repair and regeneration of multiple tissues. In a mouse model of myocardial I/R injury, intravenous injection of PINCs results in augmented cardiac function and mitigated heart remodeling, which is accompanied by the increase in cycling cardiomyocytes, activation of endogenous stem/progenitor cells, and promotion of angiogenesis. This approach represents a promising therapeutic delivery platform for treating I/R injury.
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