微泡
再灌注损伤
线粒体通透性转换孔
免疫系统
微泡
缺血
TFAM公司
线粒体
细胞生物学
外体
小RNA
医学
癌症研究
免疫学
生物
细胞凋亡
线粒体生物发生
生物化学
程序性细胞死亡
基因
心脏病学
作者
Shanshan Liu,Xinyu Xiao,Zhang La,Jianwei Wang,Zhao Wang,Haichuan Liu,Rui Liao,Liu Zhi,Mengxia Xu,Jian Guo,Baoyong Zhou,Cheng Du,Qiling Peng,Ning Jiang
出处
期刊:Theranostics
[Ivyspring International Publisher]
日期:2024-01-01
卷期号:14 (1): 116-132
摘要
Background: Therapeutic interventions such as synthetic drugs and microRNA (miR) modulators have created opportunities for mitigating hepatic ischemia/reperfusion injury (HIRI) by alleviating mitochondrial dysfunction. However, delivering multi-therapeutic ingredients with low toxicity to hepatocytes still lags behind its development. Methods: In this study, we endowed exosomes with delivery function to concentrate on hepatocytes for multidimensionally halting mitochondria dysfunction during HIRI. Concretely, exosomes were reprogrammed with a transmembrane protein CD47, which acted as a "camouflage cloak" to mimic the "don't eat me" mechanism to escape from immune surveillance. Besides, HuR was engineered bridging to the membrane by fusing with CD47 and located in the cytoplasm for miR loading. Results: This strategy successfully delivered dual payloads to hepatocytes and efficiently protected mitochondria by inhibiting the opening of mitochondrial permeability transition pore (mPTP) and upregulating mitochondrial transcription factor A (TFAM), respectively. Conclusions: The reprogramming of exosomes with CD47 and HuR for targeted delivery of CsA and miR inhibitors represents a promising therapeutic strategy for addressing HIRI. This approach shows potential for safe and effective clinical applications in the treatment of HIRI.
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