Nitric oxide (NO) possesses various functions in cardiovascular diseases; however, due to an extremely short half-life and low bioavailability, its therapeutic application is limited. In inflamed tissues, overproduced reactive oxygen species (ROS) rapidly react with the endogenous NO, reducing its bioavailability. Here, we developed a controllable NO-releasing injectable hydrogel (NO-RIG) formed by the electrostatic crosslinking between the polyion complex flower-type micelles composing of functional polymers to scavenge overproduced ROS and regulate the local NO expression level simultaneously. After the intracardiac injection to mice, NO-RIG converted to gel via physiological temperature-responsive character, distributed homogeneously, and retained in the myocardial tissue for more than 10 d. Treatment with NO-RIG remarkably decreased the infarction size and improved the heart function after myocardial infarction when compared to control injectable hydrogels, such as a simple NO-releasing or ROS-scavenging injectable gels. We found that NO-RIG treatment significantly enhanced the angiogenesis and new blood vessels formation in mice through the regulation of the NO sustained release and redox equilibrium. NO-RIG presents high potential in preventing and treating cardiovascular diseases.

一氧化氮（NO）在心血管疾病中具有多种功能；然而，由于半衰期极短且生物利用度低，其治疗应用受到限制。在发炎的组织中，过量产生的活性氧（ROS）与内源性NO迅速反应，从而降低了其生物利用度。在这里，我们开发了一种可控的可释放NO的可注射水凝胶（NO-RIG），该凝胶由功能性聚合物组成的聚离子复合物花型胶束之间的静电交联形成，以清除过量产生的ROS和同时调节局部NO的表达水平。小鼠心内注射后，NO-RIG通过生理温度响应特性转变为凝胶，均匀分布，并在心肌组织中保留10 d以上。与对照注射用水凝胶（例如简单的释放NO或清除ROS的注射凝胶）相比，用NO-RIG进行的治疗显着减少了心肌梗塞后的梗塞面积并改善了心脏功能。我们发现，NO-RIG治疗通过调节NO持续释放和氧化还原平衡，显着增强了小鼠的血管生成和新血管形成。NO-RIG在预防和治疗心血管疾病方面具有很高的潜力。我们发现，NO-RIG治疗通过调节NO持续释放和氧化还原平衡，显着增强了小鼠的血管生成和新血管形成。NO-RIG在预防和治疗心血管疾病方面具有很高的潜力。我们发现，NO-RIG治疗通过调节NO持续释放和氧化还原平衡，显着增强了小鼠的血管生成和新血管形成。NO-RIG在预防和治疗心血管疾病方面具有很高的潜力。