Hokkaido University develops artificial mitochondria "e-MITO" — Enhanced intracellular delivery and controllable function demonstrated

A research group led by Professor Yuma Yamada of the Faculty of Pharmaceutical Sciences at Hokkaido University, in collaboration with Luca Science (President and Representative Director Stig Ogata), has developed Enhanced Artificially Designed Mitochondria "e-MITO." They showed the potential of a new organelle formulation technology that controls cellular function. Their technology may be applied to cell therapy, regenerative medicine, and disease research. The results were published in the July 1st issue of Advanced Materials Interfaces.

Mitochondria are intracellular organelles responsible for energy production within cells and are deeply involved in maintaining cellular functions and regulating metabolism. The decline in mitochondrial function has been reported to be linked to aging and various diseases, and new therapeutic techniques to transplant normal mitochondria are attracting attention. Meanwhile, isolated mitochondria are unstable and vulnerable in storage or transportation, with poor delivery efficiency, which represent challenges.

The research group has been developing mitochondria-targeted nanocapsules that deliver drugs and nucleic acids to mitochondria. In this research, the group aimed to artificially design mitochondria themselves and utilize them as functional materials. Specifically, they used mitochondrial material "MRC-Q" isolated and prepared by Luca Science's proprietary technology and constructed "e-MITO" using "mitochondrial surface engineering," which involves introducing polyethylene glycol (PEG) lipids to the surface and displaying cell-penetrating peptides (CPPs) at their ends.

They delivered "e-MITO" into cells and confirmed improved cellular uptake compared with unmodified mitochondria. In those cells with "e-MITO," mitochondrial respiratory activity (oxygen consumption rate) and ATP production capacity were elevated. Furthermore, elevated mitochondrial respiratory capacity, particularly related to intracellular energy production, was observed.

The PEG protective layer improved cellular delivery capacity while minimizing the impact on mitochondrial structure. There is high hope for the development of a new research field called organelle pharmaceutics, which involves controlling cellular functions using artificially designed organelles.

Yamada said, "In developing 'e-MITO,' we struggled with delivering them to cells while maintaining the properties of mitochondria. We hope to use these results as a starting point to develop a new foundational technology for drug delivery and cell engineering that can freely regulate cellular functions."

Journal Information
Publication: Advanced Materials Interfaces
Title: CPP-PEG-Guided Surface Engineering of Mitochondria Enables Efficient Cellular Uptake and Respiratory Modulation
DOI: 10.1002/admi.70583