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Background: Micro RNA of Marsupenaeus japonicas has been known to promote apoptosis of tumor cells. However, the detailed mechanisms are not well understood. Results: Using tomographic microscope, which can detect the internal structure of cells, we observed breast tumor cells following treatment of the miRNA. Intriguingly, we found that mitochondria migrate to an adjacent tumor cells through a tunneling nanotube. To recapitulate this process, we engineered a microfluidic device through which mitochondria were transferred. We show that this mitochondrial transfer process released endonuclease G (Endo G) into tumor cells, which we referred to herein as unsealed mitochondria. Importantly, Endo G depleted mitochondria alone did not have tumoricidal effects. Moreover, unsealed mitochondria had synergistic apoptotic effects with subtoxic dose of doxorubicin thereby mitigating cardiotoxicity. Conclusions: Together, we show that the mitochondrial transfer through microfluidics can provide potential novel strategies towards tumor cell death. [ABSTRACT FROM AUTHOR]

Abstract: Lipid nanotubes interconnecting mammalian cells, sometimes referred to as tunneling nanotubes, have recently received increased attention, as their importance in intercellular transport and communication has been recognized. We present a set of microfabrication procedures for the deliberate formation of intercellular nanotube links between single mammalian cells, employing microneedle manipulation protocols, developed earlier for nanotube-vesicle networks. Cell-to-cell connections were established, and their effectiveness for intercellular transport of molecular cargo was demonstrated. We initiate transport of ions and fluorescein diphosphate, a prefluorescent enzyme substrate, between cells, and demonstrate the validity and effectiveness of artificially created nanotube connections for cell-to-cell communication. We thus provide a new experimental model for probing cell-to-cell communication, which we deem the foundation for man-made network architectures involving biological cells. This model can greatly facilitate fundamental studies of cell-to-cell communication modes, the exchange of cell constituents and components, and the dynamics of biochemical reactions in native network environments. [Copyright &y& Elsevier]