Macrophage membrane-biomimetic nanoparticles for targeted delivery of melatonin in myocardial ischemia-reperfusion injury

Myocardial ischemia-reperfusion injury (MIRI) remains a major clinical challenge following the restoration of blood flow after ischemic events in the heart. Excessive reactive oxygen species production during this process exacerbates cellular damage and impairs cardiac function. However, clinically effective and safe antioxidative treatments are yet to be developed. Melatonin is a potential endogenous antioxidant with widely reported protective effects against cardiac damage and altered physiology during I/R injury, yet its short circulation half-life and insufficient accumulation at injured sites restrict its therapeutic efficacy. To address these limitations, we developed a liposome-based biomimetic nanoparticle (NPs@MM) consisting of a liposome and a macrophage membrane shell. By inheriting the intrinsic inflammatory tropism of macrophages, NPs@MM selectively targeted injured vascular endothelium and accumulated in ischemic myocardial tissue. Moreover, melatonin release was triggered by the acidic environment at the infarcted site, enabling effective scavenging of excess ROS. The amount of NPs@MM in the infarcted myocardium was greatly increased compared with NPs alone, resulting in an effective reduction of the MIRI-induced ROS. Collectively, these findings suggest that NPs@MM enable targeted delivery of melatonin and effective attenuation of oxidative stress in the MIRI region, thereby protecting the myocardium from ROS-induced damage.