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Cited by 1,683Mitochondrial Function and PathologyMolecular Sensors and Ion DetectionNanoplatforms for cancer theranostics

Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications

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Zielonka, Jacek, Joseph, Joy, Sikora, Adam, Hardy, Micael, Ouari, Olivier, Vasquez-Vivar, Jeannette, Cheng, Gang, Lopez, Marcos +1 more·2017·Chemical Reviews
DOI 10.1021/acs.chemrev.7b00042PMC PMC5611849
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Abstract

Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the cell and mitochondrial membrane potentials, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this Review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

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  • The mitochondrion is considered a therapeutic target for cancer, cardiovascular diseases, neurological diseases, and infections because of its important functions in cell viability and its mitochondrial targeting characteristics.

    “The mitochondrion is considered a therapeutic target for a variety of diseases (cancer, cardiovascular diseases, neurological diseases, and infections), not only because of its important functions in cell viability but also because of its mitochondrial targeting characteristics (22).”

    From Recent Progress in Research on Mitochondrion-Targeted Antifungal Drugs: a Review (2023) · cites this paper as [22]

    The Introduction describes mitochondria’s roles in energy production, cell signaling, and cell death, and discusses mitochondrial targeting for neurological and cardiovascular diseases and cancer. It does not support the inclusion of infections; a search for infection found no relevant passage. The targeting characteristics discussed are properties used to deliver compounds to mitochondria, rather than characteristics of mitochondria themselves. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

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Authors
Zielonka, J., Joseph, J., Sikora, A., Hardy, M., Ouari, O., Vasquez-Vivar, J., Cheng, G., Lopez, M., & Kalyanaraman, B.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Lodz University of Technology (PL)
  • Aix Marseille Univ, CNRS, ICR, UMR 7273, Marseille 13013, France
  • Translational Biomedical Research Group, Biotechnology Laboratories, Cardiovascular Foundation of Colombia, Carrera 5a No. 6-33, Floridablanca, Santander 681003, Colombia
Corresponding author
  • Zielonka, Jacek
  • Kalyanaraman, Balaraman
ORCID
Venue
Chemical Reviews
Publisher
American Chemical Society (ACS)
Published
2017-06-27
Volume
117
Issue
15
Pages
10043-10120
ISSN
  • 0009-2665 (ISSN-L)
  • 1520-6890
DOI
10.1021/acs.chemrev.7b00042
PMC
PMC5611849
OpenAlex
W2728985030
Cited by
1,683
References
32
Citations by year
2026: 202 · 2025: 233 · 2024: 234 · 2023: 197 · 2022: 207 · 2021: 225 · 2020: 158 · 2019: 136 · 2018: 76 · 2017: 14
FWCI
9.83
Type
journal article
Language
en
Open access
Locations
  • Chemical Reviews (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HAL AMU (submittedVersion)
Funders
  • National Cancer Institute (R01 CA152810, U01 CA178960)
  • Agence Nationale de la Recherche (ANR-09-BLAN-0193-02, ANR-15-CE29-0022-01, ANR-16-CE07-0023-01)
  • Narodowe Centrum Nauki (2015/18/E/ST4/00235)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Physical Sciences › Chemistry › Spectroscopy › Molecular Sensors and Ion Detection
  • Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Keywords
mitochondria-targeted drugs, triphenylphosphonium, lipophilic cations, mitochondrial accumulation, mitochondrial membrane potential, mitochondrial targeting peptide, nanoparticle drug delivery, mitochondrial dysfunction, cancer therapy, neurodegenerative diseases
MeSH terms
Antineoplastic Agents, Humans, Mitochondria, Neoplasms, Organophosphorus Compounds, Neurodegenerative Diseases, Membrane Potential, Mitochondrial

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