Mitochondria targeted fluorogenic theranostic agents for cancer therapy

Mitochondria, an eukaryotic organelle, is regarded as the most critical target since it regulates several vital functions in cell physiology. It is the hub of metabolic activity and a source of fascination due to its role in a variety of diseases like cardiovascular, cancer and neurological disorders. Because of the structural and functional discrepancies between normal and cancerous mitochondria (respiratory rate, membrane potential, genetic mutations and energy-producing pathway), mitochondria have garnered substantial attention in cancer therapy. For delivering cytotoxins exclusively to mitochondria, several synthetic strategies are used for mitochondrial dysfunction and cell apoptosis/necrosis. Covalent binding of lipophilic cations (triphenylphosphonium ion, rhodamine, peptides etc) to the molecular-based pharmacophore is the most effective process. Significant mitochondrial accumulations (>1000 folds) can be accomplished by proper selection of cell types, their mitochondrial membrane potential and targeting unit. In this review article, we address various strategies for targeting small molecule-based theranostics to cancerous mitochondria for diagnostic and potential therapeutic purposes that have been published since 2015. Particularly, conventional chemotherapeutic drugs, photosensitizers for photodynamic and photothermal treatment, drug-free agents, intra-mitochondrial aggregation agents and their combination are among the molecular-based agents discussed. (C) 2021 Published by Elsevier B.V.

Automated summary

Mitochondria, as the most critical target in cell physiology, have attracted substantial attention in cancer therapy due to their structural and functional discrepancies between normal and cancerous cells. Various synthetic strategies are used to deliver cytotoxins exclusively to mitochondria, achieving significant mitochondrial accumulations by proper selection of cell types and targeting unit. This review article addresses different strategies for targeting cancerous mitochondria with small molecule-based theranostics for diagnostic and potential therapeutic purposes since 2015.