Trans MIT: microfluidically fabricated lipid nano capsules for robust intracellular delivery of mitochondria-derived components and metabolic enhancement

Intracellular transfer of intact mitochondria has primarily been reported as a therapeutic approach to restore cellular function; however, controlled intracellular delivery of mitochondria-derived components remains largely unexplored, particularly from a materials and manufacturing perspective. Here, we present Trans MIT, microfluidically fabricated lipid nano capsules designed for robust intracellular delivery of mitochondria-derived components. Trans MIT is constructed based on the MITO-Porter concept, a lipid-based delivery platform originally developed for mitochondrial targeting via membrane fusion, and is manufactured using a controlled microfluidic (iLiNP) process to ensure reproducible particle properties. In cultured cells, treatment with Trans MIT resulted in consistent enhancement of cellular bioenergetic function, as evidenced by increased basal and maximal oxygen consumption rates and elevated ATP levels. Metabolomic analyses further revealed activation of the tricarboxylic acid cycle and oxidative phosphorylation pathways following Trans MIT delivery. In this system, cellular uptake is mediated by an octaarginine (R8) moiety, while the fusogenic lipid envelope facilitates mitochondrial targeting of mitochondria-derived components without inducing overt cytotoxicity. The microfluidic fabrication process further supports batch-to-batch consistency and scalability. In contrast to direct addition of isolated mitochondria under specific experimental conditions, Trans MIT provides a materials-driven platform for controlled intracellular delivery of mitochondria-derived components. These results establish Trans MIT as a robust lipid nano capsule system for organelle-inspired nanomedicine and materials-based modulation of cellular metabolism.