Phosphorescent metal complexes as theranostic anticancer agents: combining imaging and therapy in a single molecule

Tan, Cai‐Ping; Zhong, Yanmei; Ji, Liang‐Nian; Mao, Zong‐Wan

doi:10.1039/d0sc06885c

Cited by 83 publications

(57 citation statements)

References 90 publications

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“…In this section, we will discuss a few prominent examples of metal-based optical theranostics with a particular emphasis on their design principle and biological studies in cells or in animals. For exhaustive examples of optical theranostics and theranostic conjugates including those of small-molecule metal-based optical theranostics, the readers are directed to consult some excellent reviews published recently [ 53–59 ]. For the sake of clarity, we have decided to classify the examples based on the metal center being employed.…”

Section: Theranostics Comprising Optical Imagingmentioning

confidence: 99%

Challenges and opportunities in the development of metal-based anticancer theranostic agents

2022

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Around 10 million fatalities were recorded worldwide in 2020 due to cancer and statistical projections estimate the number to increase by 60 % in 2040. With such a substantial rise in the global cancer burden, the disease will continue to impose a huge socio-economic burden on society. Currently, the most widely used clinical treatment modality is cytotoxic chemotherapy using platinum drugs which is used to treat variety of cancers. Despite its clinical success, critical challenges like resistance, off-target side effects and cancer variability often reduce its overall therapeutic efficiency. These challenges require faster diagnosis, simultaneous therapy and a more personalized approach towards cancer management. To this end, small-molecule ‘theranostic’ agents have presented a viable solution combining diagnosis and therapy into a single platform. In this review we present a summary of recent efforts in the design and optimization of metal-based small-molecule ‘theranostic’ anticancer agents. Importantly, we highlight the advantages of a theranostic candidate over the purely therapeutic or diagnostic agent in terms of evaluation of their biological properties.

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Section: Theranostics Comprising Optical Imagingmentioning

confidence: 99%

Challenges and opportunities in the development of metal-based anticancer theranostic agents

2022

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“…Ruthenium complexes exhibit a low general toxicity and accumulate in cancer cells due to their high rate of ligand exchange, the range of accessible oxidation states, and their ability to simulate iron binding to certain biomolecules [ 5 ]. As a result, ruthenium complexes are expected to be the next anticancer drugs [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Arene Ru(II) Complexes with Difluorinated Ligands Act as Potential Inducers of S-Phase Arrest via the Stabilization of c-myc G-Quadruplex DNA

et al. 2022

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Here, a series of half-sandwich arene Ru(II) complexes with difluorinated ligands [Ru(η6-arene)(L)Cl] (L1 = 2-(2,3-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; L2 = 2-(2,4-difluorophenyl)imidazole[4,5f][1,10]-phenanthroline; arene = benzene, toluene, and p-cymene) were synthesized and characterized. Molecular docking analysis showed that these complexes bind to c-myc G-quadruplex DNA through either groove binding or π–π stacking, and the relative difluorinated site in the main ligand plays a role in regulating the binding mode. The binding behavior of these complexes with c-myc G-quadruplex DNA was evaluated using ultraviolet–visible spectroscopy, fluorescence intercalator displacement assay, fluorescence resonance energy transfer melting assay, and polymerase chain reaction. The comprehensive analysis indicated that complex 1 exhibited a better affinity and stability in relation to c-myc G-quadruplex DNA with a DC50 of 6.6 μM and ΔTm values of 13.09 °C, than other molecules. Further activity evaluation results displayed that this class of complexes can also inhibit the growth of various tumor cells, especially complexes 3 and 6, which exhibited a better inhibitory effect against human U87 glioblastoma cells (51.61 and 23.75 μM) than other complexes, even superior to cisplatin (32.59 μM). Owing to a befitting lipophilicity associated with the high intake of drugs by tumor cells, complexes 3 and 6 had favorable lipid-water partition coefficients of −0.6615 and −0.8077, respectively. Moreover, it was found that complex 6 suppressed the proliferation of U87 cells mainly through an induced obvious S phase arrest and slight apoptosis, which may have resulted from the stabilization of c-myc G-quadruplex DNA to block the transcription and expression of c-myc. In brief, these types of arene Ru(II) complexes with difluorinated ligands can be developed as potential inducers of S-phase arrest and apoptosis through the binding and stabilization of c-myc G-quadruplex DNA, and could be used in clinical applications in the future.

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“…A systematic summary of the advances ( Jin et al, 2021 ) in phosphorescence-based ratiometric sensing of physical parameters and chemical characteristics of living systems, including bioimaging and medical therapy, was recently presented. Iridium(III), ruthenium(II), and rhenium(I) rare-earth metal complexes, phosphorescent at room temperature ( Tan et al, 2021 ) able to monitor the dynamic behavior of subcellular organelles and serving additionally as multifunctional antitumor compounds and integrating imaging and antitumor functions in a single molecule, were reported. Combination of Ir (III)–porphyrins with cell-penetrating and tumor-targeting peptides ( Koren et al, 2012 ) allows sensing the oxygen saturation in various mammalian cell types.…”

Section: Introductionmentioning

confidence: 99%

Tetrathienothiophene Porphyrin as a Metal-Free Sensitizer for Room-Temperature Triplet–Triplet Annihilation Upconversion

et al. 2022

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Optically excited triplet states of organic molecules serve as an energy pool for the subsequent processes, either photon energy downhill, such as room temperature phosphorescence, or photon energy uphill process—the triplet–triplet annihilation upconversion (TTA-UC). Manifestation of a high intersystem crossing coefficient is an unavoidable requirement for triplet state formation, following the absorption of a single photon. This requirement is even more inevitable if the excitation light is non-coherent, with moderate intensity and extremely low spectral power density, when compared with the light parameters of 1 Sun (1.5 AM). Coordination of a heavy atom increases substantially the probability of intersystem crossing. Nevertheless, having in mind the global shortage in precious and rare-earth metals, identification of metal-free organic moieties able to form triplet states becomes a prerequisite for environmental friendly optoelectronic technologies. This motivates us to synthesize a metal-free thienothiophene containing porphyrin, based on a condensation reaction between thienothiophene-2-carbaldehyde and pyrrole in an acidic medium by modified synthetic protocol. The upconversion couple tetrathienothiophene porphyrin/rubrene when excited at λ = 658 nm demonstrates bright, delayed fluorescence with a maximum emission at λ = 555 nm. This verifies our hypothesis that the ISC coefficient in thienothiophene porphyrin is efficient in order to create even at room temperature and low-intensity optical excitation densely populated organic triplet ensemble and is suitable for photon energy uphill processes, which makes this type of metal-free sensitizers even more important for optoelectronic applications.

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Phosphorescent metal complexes as theranostic anticancer agents: combining imaging and therapy in a single molecule

Abstract: The recent development in phosphorescent iridium, ruthenium and rhenium complexes as theranostic anticancer agents is summarized.

Cited by 83 publications

References 90 publications

Challenges and opportunities in the development of metal-based anticancer theranostic agents

Challenges and opportunities in the development of metal-based anticancer theranostic agents

Arene Ru(II) Complexes with Difluorinated Ligands Act as Potential Inducers of S-Phase Arrest via the Stabilization of c-myc G-Quadruplex DNA

Tetrathienothiophene Porphyrin as a Metal-Free Sensitizer for Room-Temperature Triplet–Triplet Annihilation Upconversion

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