Luo Qiao, Cheng Nianlan, Yang Yongqing, Shao Ni, Nie Tianqi, Chen Jifeng, Huang Cuiqing, Zhang Siqi, Huang Yanyu, Ieong Chon Man, Zhang Xiaokai, Hu Kuan, Xiao Zeyu, Luo Liangping
The Guangzhou Key Laboratory of Molecular and Functional Imaging for Clinical Translation, Department of Radiology and Nuclear Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China.
Guangzhou Twelfth People's Hospital, Guangzhou, 510620, China.
Mater Today Bio. 2025 May 14;32:101854. doi: 10.1016/j.mtbio.2025.101854. eCollection 2025 Jun.
Myocardial ischemia-reperfusion (I/R) injury is characterized by oxidative stress, mitochondrial dysfunction, inflammation, and fibrosis, ultimately leading to chronic cardiac dysfunction and heart failure. Current therapeutic strategies that predominantly target single biological pathways exhibit limited long-term efficacy, underscoring the necessity for multi-targeted approaches. In this study, we developed a ROS-responsive hydrogel system, S1&FT/Lipo-QCFT, tailored to deliver drugs for treating various stages of myocardial I/R injury. This system timing of drug release to achieve rapid deployment at early intervention stages and maintain sustained release thereafter. Initially, the hydrogel platform quickly releases the molecular forms of the superoxide inhibitor S1QEL1.1 and tannic acid, specifically targeting the elevated ROS levels at the I/R site to alleviate early oxidative damage and encourage macrophage polarization toward the M2 phenotype. Subsequently, the system gradually releases anti-fibrotic agent FT011, encapsulated in lipid nanocarriers, which actively counters TGF-β1-induced fibrosis and forestalls adverse ventricular remodeling, thereby enhancing long-term cardiac repair. studies demonstrated that the S1&FT/Lipo-QCFT hydrogel significantly improved cardiac function and reduced adverse ventricular remodeling. This hydrogel system provides a promising multi-targeted therapeutic strategy for comprehensive myocardial I/R injury treatment with strong potential for clinical translation.
心肌缺血再灌注（I/R）损伤的特征是氧化应激、线粒体功能障碍、炎症和纤维化，最终导致慢性心脏功能障碍和心力衰竭。目前主要针对单一生物途径的治疗策略长期疗效有限，这凸显了多靶点治疗方法的必要性。在本研究中，我们开发了一种ROS响应水凝胶系统S1&FT/Lipo-QCFT，用于递送治疗心肌I/R损伤各个阶段的药物。该系统能够控制药物释放时间，以便在早期干预阶段实现快速给药，并在随后保持持续释放。最初，水凝胶平台迅速释放超氧化物抑制剂S1QEL1.1和单宁酸的分子形式，特异性靶向I/R部位升高的ROS水平，以减轻早期氧化损伤，并促进巨噬细胞向M2表型极化。随后，该系统逐渐释放包裹在脂质纳米载体中的抗纤维化药物FT011，其可有效对抗TGF-β1诱导的纤维化，防止不良心室重构，从而增强长期心脏修复。研究表明，S1&FT/Lipo-QCFT水凝胶显著改善了心脏功能，减少了不良心室重构。这种水凝胶系统为全面治疗心肌I/R损伤提供了一种有前景的多靶点治疗策略，具有很强的临床转化潜力。
