Heme cascade-triggered nanovesicles for myocardial ischemic core delivery.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41909508.
- Also identified by DOI 10.1016/j.bioactmat.2026.03.027 and PMC identifier 13022641.
- Licence recorded as CC BY-NC-ND.
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Abstract
Myocardial ischemia-reperfusion injury (MIRI) remains a significant therapeutic challenge due to insufficient targeted drug delivery. Recognizing heme as a key endogenous signal that has yet to be utilized in delivery systems, we designed the first heme-responsive nanovesicle (DecAS-PC@NM) for lesion-specific therapy through a cascade reaction involving two functionalized phospholipids. Specifically, heme activates the artemisinin-modified phospholipid (A-PC) to generate reactive oxygen species, which oxidize the thioether structure in another phospholipid (S-PC), triggering a hydrophilic-to-hydrophobic transition and subsequent vesicle disassembly. Co-assembly with neutrophil membranes further enhances chemotaxis toward inflammatory sites. <i>In vitro</i> studies confirm the unique heme responsiveness of DecAS-PC@NM, while <i>in vivo</i> data highlight its ischemic core targeting and significant therapeutic improvement. This innovative heme-triggered phospholipid cascade offers a promising strategy for MIRI treatment.