Zhen Penghao, Jiang Qiaochu, Yu Fuchao, Xu Xuan, Wei Qin, Liu Xiaoyang, Sun Xianbao, Liang Gaolin, Tong Jiayi
Department of Cardiology, Zhongda Hospital, School of Medicine, Southeast University, 87 Dingjiaqiao, Nanjing 210009, China.
State Key Laboratory of Digital Medical Engineering, School of Biological Science and Medical Engineering, Southeast University, Nanjing 211189, China.
J Control Release. 2025 Mar 10;379:609-620. doi: 10.1016/j.jconrel.2025.01.039. Epub 2025 Jan 24.
Treatment of myocardial ischemia-reperfusion (MI/R) injury still faces the lack of clinically approved drugs. Apelin-13 is a highly promising drug candidate of MI/R injury, but hampered by its extremely short half-life in plasma. This calls for efficient and smart delivering system for Apelin-13 delivery, but has not been reported. Herein, a reactive oxygen species (ROS)-responsive hydrogelator YFF-TK-FFY is designed, which co-assembles with Apelin-13 to form the peptide hydrogel Apelin-13@Gel TK. This hydrogel responds to ROS at varying levels in the surrounding environment of MI/R and releases Apelin-13 at different rates. In an MI/R injury mouse model, Apelin-13@Gel TK rapidly releases Apelin-13 in response to the high ROS in the core area of MI/R injury, efficiently reducing cardiomyocyte apoptosis within three days. In the ROS-low border zone, Apelin-13@Gel TK provides a slow and sustained release of Apelin-13, promoting angiogenesis and lymphatic remodeling, and facilitating the resolution of inflammation in the later repair stage after MI/R injury. By offering a spatiotemporally controlled drug release in response to ROS gradients in the MI/R microenvironment, this smart hydrogel presents a promising therapeutic strategy for effective treatment of MI/R injury.
心肌缺血再灌注（MI/R）损伤的治疗仍然面临着缺乏临床批准药物的问题。Apelin-13是一种极有前景的用于治疗MI/R损伤的候选药物，但因其在血浆中的半衰期极短而受到阻碍。这就需要一种高效且智能的给药系统来递送Apelin-13，但目前尚未见报道。在此，设计了一种活性氧（ROS）响应性水凝胶剂YFF-TK-FFY，它与Apelin-13共同组装形成肽水凝胶Apelin-13@Gel TK。这种水凝胶在MI/R的周围环境中对不同水平的ROS做出响应，并以不同速率释放Apelin-13。在MI/R损伤小鼠模型中，Apelin-13@Gel TK响应MI/R损伤核心区域的高ROS而迅速释放Apelin-13，在三天内有效减少心肌细胞凋亡。在ROS水平较低 的边缘区域，Apelin-13@Gel TK缓慢持续释放Apelin-13，促进血管生成和淋巴管重塑，并在MI/R损伤后的后期修复阶段促进炎症消退。通过响应MI/R微环境中的ROS梯度提供时空可控的药物释放，这种智能水凝胶为有效治疗MI/R损伤提供了一种有前景的治疗策略。
