Delivery of mitochondria via extracellular vesicles - A new horizon in drug delivery

Abstract

The field of drug delivery has made tremendous advances in increasing the therapeutic potential of a variety of drug candidates spanning from small molecules to large molecular biologics such as nucleic acids, proteins, etc. Extracellular vesicles (EVs) are mediators of intercellular communication and carry a rich cocktail of innate cargo including lipids, proteins and nucleic acids. EVs are a promising class of natural, cell-derived carriers for drug delivery. EVs of particle diameters <200 nm are referred to as small EVs (sEVs) and medium-to-larger particles of diameters >200 nm are referred to as m/lEVs. The m/lEVs naturally incorporate mitochondria during their biogenesis. In this Oration, I will discuss the potential of m/lEVs as carriers for the delivery of healthy and functional mitochondria. Mitochondrial damage and dysfunction play a causal role in multiple pathologies such as neurodegenerative diseases, cardiovascular and metabolic diseases-suggesting that m/lEV-mediated mitochondria delivery can be of broad biomedical significance. A major advantage of harnessing m/lEVs is that the delivered mitochondria are capable of using endogenous mechanisms for repairing the cellular damage. I will highlight the delivery potential of m/lEVs based on the studies we have conducted so far and discuss unaddressed issues towards their development as a novel class of mitochondria carriers.

Keywords: Blood-brain barrier; Medium-to-large extracellular vesicles; Mitochondria delivery; Neurodegenerative diseases; Small extracellular vesicles; Stroke.