Cellular localisation of structurally diverse diphenylacetylene fluorophores

Chisholm, David; Hughes, Joshua G; Blacker, Thomas S.; Humann, Rachel; Adams, Candace; Callaghan, Daniel J.; Pujol, Alba; Lembicz, Nicola K.; Bain, Angus J.; Girkin, John M.; Ambler, Carrie A.; Whiting, Andrew

doi:10.1039/d0ob01153c

Cited by 7 publications

(7 citation statements)

References 38 publications

(55 reference statements)

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“…S19–S22 , DCM-DH and Golgi Tracker demonstrated the best fluorescence overlap with a Pearson’s coefficient of 0.892 and 0.949, respectively, while with other organelle tracker, with Pearson’s coefficient from 0.001 to 0.766. The specific targeting of DCM-DH to the Golgi apparatus could be attributed to its lipophilicity and the –CN group, which was an effective Golgi-targeted moiety 33 – 35 . The lipophilicity of compounds played a critical role in their cell uptake and distribution in subcellular organelles, as reported in previous studies.…”

Section: Resultsmentioning

confidence: 99%

Golgi-targeting viscosity probe for the diagnosis of Alzheimer’s disease

Wu,

Zhao,

Zhang

et al. 2024

Sci Rep

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Early diagnosis and intervention of Alzheimer’s disease (AD) are particularly important to delay the pathological progression. Although fluorescent probes have been widely employed for investigating and diagnosing AD, their biological applications are significantly restricted due to the low penetration ability of the blood–brain barrier (BBB) in vivo. In this study, we reported the first Golgi-targeted two-photon (TP) fluorescent probe, DCM-DH, for detecting viscosity in the Golgi apparatus. The probe was rationally designed to exhibit superior analytical performance including high sensitivity, specific Golgi-targeting, efficient BBB penetration ability, and deep tissue penetration (247 μm) in the brains of AD model mice. Using the probe, we demonstrated that the fluorescence intensity in the human liver cancer cell (HepG2 cells) was higher than that of human normal liver cell (LO2 cells), and the brain viscosity of AD model mice increased significantly. We anticipate that this competent tool could be easily extended to other AD biomarkers for fundamental research on this detrimental disease.

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Section: Resultsmentioning

confidence: 99%

Golgi-targeting viscosity probe for the diagnosis of Alzheimer’s disease

Wu,

Zhao,

Zhang

et al. 2024

Sci Rep

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“…Firstly, we tested the lipophilicity of all compounds (Supplementary Fig. 29 , Supplementary Table 2 ) because of lipophilicity was reported to play an important role in the cell uptake and distribution of compounds in subcellular organelles 40 . The log P O/W values of each compound were determined to be 1.764, 1.581, 2.694 and 2.201 for TPE-PyT-CPS, TPE-T-CPS, TPE-PyT-CP and TPE-PyT-PS, respectively.…”

Section: Resultsmentioning

confidence: 99%

Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy

et al. 2022

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Golgi apparatus (GA) oxidative stress induced by in situ reactive oxygen species (ROS) could severely damage the morphology and function of GA, which may open up an avenue for effective photodynamic therapy (PDT). However, due to the lack of effective design strategy, photosensitizers (PSs) with specific GA targeting ability are in high demand and yet quite challenging. Herein, we report an aggregation-induced emission luminogen (AIEgen) based PS (TPE-PyT-CPS) that can effectively target the GA via caveolin/raft mediated endocytosis with a Pearson correlation coefficient up to 0.98. Additionally, the introduction of pyrene into TPE-PyT-CPS can reduce the energy gap between the lowest singlet state (S1) and the lowest triplet state (T1) (ΔEST) and exhibits enhanced singlet oxygen generation capability. GA fragmentation and cleavage of GA proteins (p115/GM130) are observed upon light irradiation. Meanwhile, the apoptotic pathway is activated through a crosstalk between GA oxidative stress and mitochondria in HeLa cells. More importantly, GA targeting TPE-T-CPS show better PDT effect than its non-GA-targeting counterpart TPE-PyT-PS, even though they possess very close ROS generation rate. This work provides a strategy for the development of PSs with specific GA targeting ability, which is of great importance for precise and effective PDT.

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“…To this end, the photosensitizer LightOx58 and a spectrally distinct ROS reporter, CellROX, were used in conjunction within HaCaT cells. LightOx58 possesses a highly lipophilic structure that enables rapid entry into mammalian cells and has been shown to localize primarily at organelle membranes and lipid droplets (de Pablo et al, 2018;Chisholm et al, 2019Chisholm et al, , 2020. Activation at 405 nm elicits the local generation of ROS in cells, oxidizing CellROX and, thus, enabling local detection of ROS at Ex/Em = 633/665 nm.…”

Section: Localized Ros Quantificationmentioning

confidence: 99%

Bullseye Analysis: A Fluorescence Microscopy Technique to Detect Local Changes in Intracellular Reactive Oxygen Species (ROS) Production

Hughes

Chisholm

Whiting

et al. 2022

Microscopy and Microanalysis

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Reactive oxygen species (ROS) are naturally produced compounds that play important roles in cell signaling, gene regulation, and biological defense, including involvement in the oxidative burst that is central to the anti-microbial actions of macrophages. However, these highly reactive, short-lived radical species also stimulate cells to undergo programmed cell death at high concentrations, as well as causing detrimental effects such as oxidation of macromolecules at more moderate levels. Imaging ROS is highly challenging, with many researchers working on the challenge over the past 10–15 years without producing a definitive method. We report a new fluorescence microscopy-based technique, Bullseye Analysis. This methodology is based on concepts provided by the FRAP (Fluorescence Recovery after Photobleaching) technique and refined to evidence the spatiotemporal production of ROS, and the subsequent consequences, on a subcellular scale. To exemplify the technique, we have used the ROS-reporter dye, CellROX, and the ROS-inducing photosensitizer, LightOx58, a potent source of ROS compared with UV irradiation alone. Further validation of the technique was carried out using differing co-stains, notably Mitotracker and JC-1.

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Cellular localisation of structurally diverse diphenylacetylene fluorophores

Abstract: The cellular localisation of diphenylacetylene fluorophores can be influenced by modifying their structure, modulating lipophilicity and incorporating ionisable groups.

Cited by 7 publications

References 38 publications

Golgi-targeting viscosity probe for the diagnosis of Alzheimer’s disease

Golgi-targeting viscosity probe for the diagnosis of Alzheimer’s disease

Golgi apparatus-targeted aggregation-induced emission luminogens for effective cancer photodynamic therapy

Bullseye Analysis: A Fluorescence Microscopy Technique to Detect Local Changes in Intracellular Reactive Oxygen Species (ROS) Production

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