Heme cascade-triggered nanovesicles for myocardial ischemic core delivery.

Chen, Hui; Yang, Ying; Aikebaier, Mirenuer; Wang, Haoran; Zheng, Lan; Zhang, Yifeng; Zha, Qing; Shan, Shuyao et al. · Bioact Mater · 2026

basic_science · Level V

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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.