Mitochondrial transplantation is an important therapeutic strategy for restoring energy supply in patients with ischaemic heart disease (IHD); however, it is limited by the invasiveness of the transplantation method and loss of mitochondrial activity. Here we report successful mitochondrial transplantation by oral administration for IHD therapy. A nitric-oxide-releasing nanomotor is modified on the mitochondria surface to obtain nanomotorized mitochondria with chemotactic targeting ability towards damaged heart tissue due to nanomotor action. The nanomotorized mitochondria are packaged in enteric capsules to protect them from gastric acid erosion. After oral delivery the mitochondria are released in the intestine, where they are quickly absorbed by intestinal cells and secreted into the bloodstream, allowing delivery to the damaged heart tissue. The regulation of disease microenvironment by the nanomotorized mitochondria can not only achieve rapid uptake and high retention of mitochondria by damaged cardiomyocytes but also maintains high activity of the transplanted mitochondria. Furthermore, results from animal models of IHD indicate that the accumulated nanomotorized mitochondria in the damaged heart tissue can regulate cardiac metabolism at the transcriptional level, thus preventing IHD progression. This strategy has the potential to change the therapeutic strategy used to treat IHD.

线粒体移植是恢复缺血性心脏病（IHD）患者能量供应的重要治疗策略；然而，它受到移植方法的侵入性和线粒体活性丧失的限制。在这里，我们报告了通过口服给药成功进行线粒体移植治疗 IHD 的情况。在线粒体表面修饰释放一氧化氮的纳米马达，以获得纳米马达化的线粒体，由于纳米马达的作用，具有针对受损心脏组织的趋化靶向能力。纳米机动线粒体被包装在肠溶胶囊中，以保护它们免受胃酸侵蚀。口服给药后，线粒体在肠道中释放，很快被肠细胞吸收并分泌到血液中，从而输送到受损的心脏组织。纳米机动线粒体对疾病微环境的调节不仅可以实现受损心肌细胞对线粒体的快速摄取和高度保留，而且可以维持移植线粒体的高活性。此外，IHD动物模型的结果表明，受损心脏组织中积累的纳米马达化线粒体可以在转录水平上调节心脏代谢，从而阻止IHD进展。该策略有可能改变 IHD 的治疗策略。