Heme cascade-triggered nanovesicles for myocardial ischemic core delivery

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Cardiovascular Research

Background:

• Myocardial ischemia-reperfusion injury (MIRI) presents a major therapeutic hurdle.
• Current drug delivery methods for MIRI lack sufficient targeting efficiency.
• Heme, an endogenous signal, has not been exploited for targeted drug delivery systems.

Purpose of the Study:

• To design and evaluate the first heme-responsive nanovesicle (DecAS-PC@NM) for lesion-specific MIRI therapy.
• To leverage a heme-triggered phospholipid cascade for controlled drug release.
• To enhance nanovesicle accumulation at inflammatory sites.

Main Methods:

• Designed DecAS-PC@NM using two functionalized phospholipids: artemisinin-modified phospholipid (A-PC) and a thioether-containing phospholipid (S-PC).
• Investigated heme-induced cascade reaction: heme activates A-PC to produce reactive oxygen species, which oxidize S-PC, causing vesicle disassembly.
• Co-assembled nanovesicles with neutrophil membranes to enhance chemotaxis.
• Conducted in vitro and in vivo studies to assess heme responsiveness, targeting, and therapeutic efficacy.

Main Results:

• DecAS-PC@NM demonstrated specific responsiveness to heme in vitro.
• In vivo studies confirmed efficient targeting to the ischemic core of the injured heart.
• Significant therapeutic improvements were observed in MIRI treatment models.

Conclusions:

• The developed heme-triggered phospholipid cascade is a novel and effective strategy for MIRI treatment.
• DecAS-PC@NM offers enhanced lesion-specific drug delivery, overcoming limitations of current therapies.
• This approach holds promise for advancing cardiovascular regenerative medicine.