Nanomedicines for Subcellular Targeting: The Mitochondrial Perspective

Background: Over the past decade, there has been a surge in the number of mitochondrialactive therapeutics for conditions ranging from cancer to aging. Subcellular targeting interventions can modulate adverse intracellular processes unique to the compartments within the cell. However, there is a dearth of reviews focusing on mitochondrial nano-delivery, and this review seeks to fill this gap with regards to nanotherapeutics of the mitochondria. Methods: Besides its potential for a higher therapeutic index than targeting at the tissue and cell levels, subcellular targeting takes into account the limitations of systemic drug administration and significantly improves pharmacokinetics. Hence, an extensive literature review was undertaken and salient information was compiled in this review. Results: From literature, it was evident that nanoparticles with their tunable physicochemical properties have shown potential for efficient therapeutic delivery, with several nanomedicines already approved by the FDA and others in clinical trials. However, strategies for the development of nanomedicines for subcellular targeting are still emerging, with an increased understanding of dysfunctional molecular processes advancing the development of treatment modules. For optimal delivery, the design of an ideal carrier for subcellular delivery must consider the features of the diseased microenvironment. The functional and structural features of the mitochondria in the diseased state are highlighted and potential nano-delivery interventions for treatment and diagnosis are discussed. Conclusion: This review provides an insight into recent advances in subcellular targeting, with a focus on en route barriers to subcellular targeting. The impact of mitochondrial dysfunction in the aetiology of certain diseases is highlighted, and potential therapeutic sites are identified.