Drug delivery systems for mitochondrial targeting

Mitochondria are essential organelles involved in both physiological and pathological processes. Dysfunctions in their activity, caused by gene mutations in mitochondrial or nuclear DNA or by other factors, can lead to a broad spectrum of primary and secondary mitochondrial diseases, characterized by diverse symptoms and clinical outcomes. Given the crucial role of this organelle in cellular life, the development of mitochondria-targeted delivery systems is essential to restore its function and offers a significant advantage in the treatment of mitochondria-related diseases, such as oxidative stress-induced conditions, and neurological disorders. Mitochondria can also be targeted in anticancer therapies to induce the death of tumor cells. Notwithstanding the variety of strategies linked to a mitochondrial-targeted therapy, reaching this organelle requires overcoming several biological barriers, ultimately mitochondrial membrane. A promising strategy in this regard is to use nanoparticles functionalized with specific ligands to direct the delivery of material to the mitochondrion. This review examines most recent advancements in nanosystem-based approaches for targeted delivery of nucleic acid therapeutics, including DNA and RNA, and small molecule drugs to this organelle. Overall, rationally designed nanomedicines that target mitochondria hold significant promise for precise therapeutic delivery at the subcellular level.