Mitochondria‐Targeting IR‐780 Dye and Its Derivatives: Synthesis, Mechanisms of Action, and Theranostic Applications

Abstract

Mitochondria are important targets in diverse physiological and pathological conditions associated with cell survival and death. The characterization of mitochondria‐targeting agents is highly useful to the understanding of mitochondrial functions and the development of targeted therapeutic strategies. IR‐780, a prototypical near‐infrared (NIR) heptamethine cyanine dye, has been recently identified as the first mitochondria‐targeting multifunctional NIR dye, it has excellent optical imaging and therapeutic properties and is receiving increasing attention in the field of NIR theranostic applications. Although the targeting mechanisms of IR‐780 dye remain to be fully identified, emerging studies have shown that the targeting process is glycolysis dependent. Therefore, it may represent a new tool to further understand and advance the field of mitochondrial medicine and glycolytic metabolism. Several types of nanostructures also have been developed to encapsulate and deliver IR‐780 dye and its derivatives for therapeutic purposes to improve their bioavailablity and potential toxicity. IR‐780 dye and its derivatives have broadened the concept of targeted imaging and therapy and have shown promise in potential applications. In consideration of the urgent need and rapid development of targeted theranostics, the recent progress on the synthesis, mechanisms of actions, and potential applications of IR‐780‐based heptamethine dyes and nanostructures for multimodal targeted imaging and therapy is reviewed.

Development of a Neutral Diketopyrrolopyrrole Phosphine Oxide for the Selective Bioimaging of Mitochondria at the Nanomolar Level

“…The mitochondrion, which is structurally characterised by a double membrane separated by the intermembrane space, exhibits a highly negative transmembrane potential as a result of the process of mitochondrial respiration whereby the proton pumps in the inner mitochondrial membrane transport protons onto the intermembrane space . This large potential distinguishes it from other subcellular organelles and has inspired the successful development of optically active probes that exploit it selectively.…”

“…Currently, a range of diagnostic imaging techniques, such as radioisotope labelling, magnetic resonance imaging and positron emission tomography, are employed for monitoring subcellular organelles . Recently, approaches exploiting fluorescence emission have been developed for the investigation of specific organelles such as mitochondria, representing a powerful class of imaging strategies, on account of their ability to translate molecular recognition into highly discriminative and easily detected optical signals …”

Mitochondria-targeted and ultrasound-responsive nanoparticles for oxygen and nitric oxide codelivery to reverse immunosuppression and enhance sonodynamic therapy for immune activation

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Improvement of obesity-associated disorders by a small-molecule drug targeting mitochondria of adipose tissue macrophages

“…1g ). Lipophilic cationic property of NIR fluorescent dye is necessary for targeting mitochondria, which explains mitochondria-preferential accumulation of IR-61 32 – 34 . Concurrently, we confirmed that IR-61 was distributed particularly in the mitochondria of ATMs (Supplementary Fig.…”