Zhao Xueli, Qin Yuze, Li Bowen, Wang Yue, Liu Jiao, Wang Bo, Zhao Jia, Yin Jiaqi, Zhang Lanlan, Li Jing, Huang Junzhe, Chen Kun, Liu Liwen, Wu Yuanming
Department of Biochemistry and Molecular Biology, Shaanxi Provincial Key Laboratory of Clinical Genetics, School of Basic Medicine, Fourth Military Medical University, Xi'an, 710032, China.
Department of Ultrasound, Xijing Hypertrophic Cardiomyopathy Center, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, China.
J Nanobiotechnology. 2025 Jan 9;23(1):10. doi: 10.1186/s12951-024-03083-2.
Cardiac fibrosis plays a critical role in the progression of various forms of heart disease, significantly increasing the risk of sudden cardiac death. However, currently, there are no therapeutic strategies available to prevent the onset of cardiac fibrosis.
Here, biomimetic ATP-responsive nanozymes based on genetically engineered cell membranes are adapted to specifically recognize activated cardiac fibroblasts (CFs) for the treatment of cardiac fibrosis. By fusing the anti-FAP CAR genetically engineered cell membrane to zeolitic imidazole frameworks-90 (zif-90) cores loaded with antioxidant nanozymes CeO and siCTGF (siRNA targeting CTGF), these nanoparticles, called FM@zif-90/Ce/siR NPs, are demonstrated to effectively reduce the accumulation of myofibroblasts and the formation of fibrotic tissue, while restoring cardiac function.
These findings demonstrate that the combination of CeO and siCTGF has a beneficial curative effect on cardiac fibrosis, with significant translational potential.
心脏纤维化在各种形式的心脏病进展中起关键作用，显著增加心脏性猝死的风险。然而，目前尚无可用的治疗策略来预防心脏纤维化的发生。
在此，基于基因工程细胞膜的仿生ATP响应纳米酶被用于特异性识别活化的心脏成纤维细胞（CFs）以治疗心脏纤维化。通过将抗FAP嵌合抗原受体（CAR）基因工程细胞膜与负载抗氧化纳米酶CeO和siCTGF（靶向CTGF的小干扰RNA）的沸石咪唑框架-90（zif-90）核心融合，这些被称为FM@zif-90/Ce/siR NPs的纳米颗粒被证明能有效减少肌成纤维细胞的积累和纤维化组织的形成，同时恢复心脏功能。
这些发现表明CeO和siCTGF的组合对心脏纤维化具有有益的治疗效果，具有显著的转化潜力。
