Artificial Mitochondrial Nanorobots Deliver Energy In Vivo by Oral Administration.

Delivering energy in vivo is essential for treating mitochondrial damage-related diseases. Current methods, including natural mitochondrial transplantation and artificial energy delivery systems, lack non-destructive, external energy-free, and clinically viable potential solutions. Here, artificial mitochondrial nanorobots (AMNs) carrying high-energy phosphate bonds rebuild the in vivo energy supply system to provide energy. Using ischemic heart disease (IHD) as an energy-deficient disease model and the oral route, which has high patient compliance and facilitates long-term administration, to investigate the therapeutic efficacy of AMNs. AMNs remain stable in the gastrointestinal tract, cross the intestinal barrier via a barrier-crossing unit, and target damaged heart tissue and cardiomyocytes using a motion unit chemotactically. Intracellularly, their energy-generating unit provides high-energy phosphate bonds for ATP synthesis (duration 12 h), while synergistically reducing inflammation and restoring cell viability. At the same frequency of administration, oral AMNs (50 mg kg-1) match intravenous AMNs (10 mg kg-1) in therapeutic efficacy, offering a convenient approach to improving cardiac function. Transcriptomics confirm that 200 µg AMNs emulate 5 × 10⁶ natural mitochondria, restoring energy metabolism and structural function in damaged hearts at the genetic level. This innovative design opens a new pathway for the construction of artificial energy delivery systems in vivo.