Near-infrared emitting fluorescent homobimetallic gold(I) complexes displaying promising in vitro and in vivo therapeutic properties

Lescure, Robin; Privat, Malorie; Pliquett, Jacques; Massot, Aurélie; Baffroy, Océane; Busser, Benoît; Bellaye, Pierre-Simon; Collin, Bertrand; Denat, Franck; Bettaı̈eb, Ali; Sancey, Lucie; Paul, Catherine; Goze, Christine; Bodio, Ewen

doi:10.1016/j.ejmech.2021.113483

Cited by 13 publications

(20 citation statements)

References 49 publications

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“…14,20 Their main limitation is their poor water solubility, but, recently, we succeeded in developing a strategy to water-solubilize them by substituting the fluorine atoms on the boron by ammonium groups. 20,21 We already proved that the resulting water-soluble aza-BODIPY, which we called Wazaby (for Water-soluble aza-BODIPY dyes), was chemically and photochemically stable and could be bioconjugated to an antibody, 21 to a metallodrug, 22 or to an MRI probe. 23 In order to investigate further the potential of the Wazabys, we aimed at constructing a SPECT/OI MOMIP, based on an aza-BODIPY platform, which presents a functionalization site for the introduction of a chelating agent for radiolabeling, and another one for the introduction of a bioconjugatable handle.…”

Section: ■ Introductionmentioning

confidence: 99%

Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore

et al. 2021

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A water-soluble fluorescent aza-BODIPY platform (Wazaby) was prepared and functionalized by a polyazamacrocycle agent and a bioconjugable arm. The resulting fluorescent derivative was characterized and bioconjugated onto a trastuzumab monoclonal antibody as a vector. After bioconjugation, the imaging agent appeared to be stable in serum (>72 h at 37 °C) and specifically labeled HER-2-positive breast tumors slices. The bioconjugate was radiolabeled with [111In] indium and studied in vivo. The developed monomolecular multimodal imaging probe (MOMIP) is water-soluble and chemically and photochemically stable, emits in the near infrared (NIR) region (734 nm in aqueous media), and displays a good quantum yield of fluorescence (around 15%). Single-photon emission-computed tomography and fluorescence imaging have been performed in nude mice bearing HER2-overexpressing HCC1954 human breast cancer xenografts and have evidenced the good tumor targeting of the [111In] In bimodal agent. Finally, the proof of concept of using it as a new tool for fluorescence-guided surgery has been shown.

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Section: ■ Introductionmentioning

confidence: 99%

Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore

et al. 2021

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“…Bodio et al . recently reported three near-infrared (NIR) optical theranostic systems comprising of Au(I) as therapeutic unit and aza-BODIPY as imaging unit ( 19a - 19c , Figure 5 ) [ 98 ]. In contrast to the above discussed example, these molecules contain an organic fluorophore.…”

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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“…[8][9][10][11][12][13][14][15][16][17][18][19][20] In our case, we are interested in gold salts. [21][22][23][24] They have been used since ancient times and are still under investigation today. Indeed, gold complexes have been exploited in modern medicine to fight against parasitic and bacterial infection, or inflammation phenomena.…”

Section: Introductionmentioning

confidence: 99%

“…[36][37][38][39][40] Thus, for the past ten years, we have been developing various gold complexes with a preference for phosphine-gold derivative, [41][42][43][44][45][46] and, if possible, complexes, which can be tracked by optical imaging. [18,21,23,[47][48][49][50][51][52] The development of such trackable therapeutics enabled us to get crucial information on the behavior of such new therapeutics in vitro. In particular, we developed a smart fluorescent "ON/OFF" probe.…”

Section: Introductionmentioning

confidence: 99%

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Conception and Evaluation of Fluorescent Phosphine‐Gold Complexes: From Synthesis to in vivo Investigations

Rousselle¹,

Massot

Privat

et al. 2022

ChemMedChem

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A phosphine gold(I) and phosphine‐phosphonium gold(I) complexes bearing a fluorescent coumarin moiety were synthesized and characterized. Both complexes displayed interesting photophysical properties: good molar absorption coefficient, good quantum yield of fluorescence, and ability to be tracked in vitro thanks to two‐photon imaging. Their in vitro and in vivo biological properties were evaluated onto cancer cell lines both human and murine and into CT26 tumor‐bearing BALB/c mice. They displayed moderate to strong antiproliferative properties and the phosphine‐phosphonium gold(I) complex induced significant in vivo anti‐cancer effect.

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Near-infrared emitting fluorescent homobimetallic gold(I) complexes displaying promising in vitro and in vivo therapeutic properties

Cited by 13 publications

References 49 publications

Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore

Development of an Easily Bioconjugatable Water-Soluble Single-Photon Emission-Computed Tomography/Optical Imaging Bimodal Imaging Probe Based on the aza-BODIPY Fluorophore

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

Conception and Evaluation of Fluorescent Phosphine‐Gold Complexes: From Synthesis to in vivo Investigations

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