The myocardial ischemia-reperfusion injury (MIRI) is an acute and serious disease with complex pathogenesis, which is intricately associated with oxidative stress, calcium overload, and inflammation. Currently, widely utilized antioxidant or anti-inflammatory strategies present challenges in effectively reversing tissue damage. In this study, a biomimetic targeted mesoporous polydopamine nanoparticle (MR/B@PM) loaded with rapamycin (RAPA) and calcium chelating agent (BAPTA-AM) was successfully constructed, and precise delivery was achieved by a platelet membrane (PM). MR/B@PM facilitated targeted delivery to cardiomyocytes (26-fold) and enhanced intracellular uptake (1.75-fold) compared to MR/B, which was mainly attributed to the natural infarct homing ability of PM and the high affinity between PM and myocardial cells. MR/B@PM significantly inhibited 85.78% of hypoxia-reoxygenation (H/R)-induced cell apoptosis and exerted favorable inhibitory effects on myocardial injury with reduced CK-MB and LDH to 7.61 and 19.43 pg/mL compared to the H/R group. It was proved that MPDA acted as a combined effect with BAPTA-AM and RAPA to inhibit cardiomyocyte apoptosis and modulate the inflammatory response by scavenging ROS and reducing calcium overload. And in the MIRI rat model, MR/B@PM has been demonstrated to significantly reduce serum levels of CK-MB and LDH, while effectively suppressing inflammatory responses. Notably, MR/B@PM effectively reduced infarct size to 19.51% and prevented cardiac remodeling caused by MIRI. This designed nanoplatform comprehensively regulated the multiple pathogenesis of MIRI, which provided an effective strategy and mechanism for the treatment of MIRI.
Liu et al. (Fri,) studied this question.