A Novel Ultrasound-Responsive Biomimetic Nanoparticle for Targeted Delivery and Controlled Release of Nitric Oxide to Attenuate Myocardial Ischemia Reperfusion Injury

Targeted and controlled nitric oxide (NO) release is critical due to an extremely short half life and low bioavailability for treating cardiovascular diseases. To address this challenge, various sustained-release precursors and NO donors activated by light, enzyme, or pH are developed. However, their efficacy is limited by the deep location and rapid blood flow of the heart. Herein, a platelet membrane-coated nanoparticle (B-P@PLT) is designed with a polymeric core loaded with BNN6, an ultrasound-responsive NO donor, for the targeted treatment of myocardial ischemia reperfusion injury (MIRI). B-P@PLT can specifically target the ischemic myocardium and release NO during ultrasound (US) irradiation, thereby increasing the local concentration of NO. B-P@PLT + US shows promising results in promoting angiogenesis, reducing reactive oxygen species production, protecting cardiomyocytes both in vitro and in vivo, and ultimately decreasing cardiac injury and improving heart function in MIRI mice. These findings demonstrate a simple and noninvasive strategy for targeted delivery and controlled release of NO, highlighting its potential therapeutic application in MIRI.