A method for screening mitochondrial fusogenic envelopes for use in mitochondrial drug delivery.

Various types of mitochondrial dysfunctions have been implicated in a variety of human diseases. This suggests that mitochondria would be promising therapeutic drug targets and mitochondrial therapy would be expected to be useful for the treatment of various diseases. We have already reported the development of a MITO-Porter, a liposome-based nano-carrier that delivers its cargo to mitochondria via a membrane-fusion mechanism. In our strategy for delivering cargos to mitochondria using a MITO-Porter, the carriers must fuse with the organelle membrane. Here we report on methodology for screening various types of lipid envelopes that have the potential for fusing with a mitochondrial membrane. The method involves monitoring the cancellation of fluorescence resonance energy transfer (FRET) and evaluating membrane fusion between the carriers and mitochondria in living cells by FRET analysis using a spectral imaging fluorescent microscopy system.