Liposomes, as nanocarriers for therapeutics, are a prominent focus in translational medicine. Given their biocompatibility, liposomes are suitable drug delivery systems rendering highly efficient therapeutic outcomes with minimal off-site toxicity. In different scenarios of human disease, it is essential not only to maintain therapeutic drug levels but also to target them to the appropriate intracellular compartment. Mitochondria regulate cellular signalling, calcium balance, and energy production, playing a crucial role in various human diseases. The notion of focusing on mitochondria for targeted drug delivery was proposed several decades ago, yet the practical application of this idea and its translation to clinical use is still in development. Mitochondrial-targeted liposomes offer an alternative to standard drug delivery systems, potentially reducing off-target interactions, side effects, and drug dosage or frequency. To advance this field, it is imperative to integrate various disciplines such as efficient chemical design, pharmacology, pharmaceutics, and cell biology. This review summarises scientific advances in the design, development and characterisation of novel liposome-based drug delivery systems targeting the mitochondria while revisiting their translational potential.
Keywords: Nanocarriers; liposomes; mitochondria; mitochondrial dysfunction; targeted drug delivery.
Several mitochondrial targeting moieties such as lipophilic cations, plant-based and peptide-based targeting approaches have been explored for the functionalisation of liposomal formulations allowing the delivery of hydrophobic drugs while improving their in vivo half-life.Amongst these targeting moieties, lipophilic cations, triphenyl phosphonium (TPP+) and dequalinium (DQA) are the most explored. However, recently developed mito-porters have gained traction in translational medicine beyond gene therapy.Research is still required to meticulously design a liposome formulation capable of targeting mitochondria as well as homing in on the specific organ of interest overcoming the challenge of crossing human barriers such as the blood-brain barrier.