62,723 research outputs found

    Structurally optimised BODIPY derivatives for imaging of mitochondrial dysfunction in cancer and heart cells

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    The structural features required for mitochondrial uptake of BODIPY-based optical imaging agents have been explored. The first derivatives of this class of dyes shown to have mitochondrial membrane potential-dependent uptake in both cancer and heart cells have been developed

    Recent progress in mitochondria-targeted drug and drug-free agents for cancer therapy

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    The mitochondrion is a dynamic eukaryotic organelle that controls lethal and vital functions of the cell. Being a critical center of metabolic activities and involved in many diseases, mitochondria have been attracting attention as a potential target for therapeutics, especially for cancer treatment. Structural and functional differences between healthy and cancerous mitochondria, such as membrane potential, respiratory rate, energy production pathway, and gene mutations, could be employed for the design of selective targeting systems for cancer mitochondria. A number of mitochondria-targeting compounds, including mitochondria-directed conventional drugs, mitochondrial proteins/metabolism-inhibiting agents, and mitochondria-targeted photosensitizers, have been discussed. Recently, certain drug-free approaches have been introduced as an alternative to induce selective cancer mitochondria dysfunction, such as intramitochondrial aggregation, self-assembly, and biomineralization. In this review, we discuss the recent progress in mitochondria-targeted cancer therapy from the conventional approach of drug/cytotoxic agent conjugates to advanced drug-free approaches

    Dual-modal SERS/fluorescence AuNP probe for mitochondrial imaging

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    A novel SERS/fluorescent multimodal imaging probe for mitochondria has been synthesised using 12 nm diameter gold nanoparticles (AuNP) surface functionalised with a rhodamine thiol derivative ligand. The normal pH dependant acidic fluorescence of the rhodamine based ligand is inversed when conjugated with the AuNP and higher emission intensity is observed at basic pH. This switch correlates to a pKa at pH 6.62, which makes it an ideal candidate for a pH sensitive imaging probe in the biological range (6.5-7.4). The observed pH sensitivity when attached to the AuNP is thought to be due to the formation of a spirolactam ring on the ligand, going from positively charged (+18 mV) to negatively charged (-60 mV) as the pH is changed from acidic to basic. Additionally, conjugation of the ligand to the AuNP serves to enhance the Raman signal of the rhodamine ligand through Surface Enhanced Raman Scattering (SERS). Confocal microscopy has shown that the probe enters HEK293 (kidney), A2780 (ovarian cancer) and Min6 (pancreatic beta) cells within an hour and a half incubation time. The probe was shown to localise in the mitochondria, thus providing a novel pH dependent SERS/fluorescent multimodal imaging probe for mitochondria

    Lanthanide(III) complexes of rhodamine-DO3A conjugates as agents for dual-modal imaging

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    Two novel dual-modal MRI/optical probes based on a rhodamine-DO3A conjugate have been prepared. The bis aqua-Gd(III) complex Gd.L1 and mono aqua-Gd(III) complex Gd.L2 behave as dual-modal imaging probes (r1 = 8.5 and 3.8 mM-1s-1 for Gd.L1 and Gd.L2 respectively; λex = 560 nm and λem = 580 nm for both complexes). The rhodamine fragment is pH sensitive and upon lowering of pH an increase in fluorescence intensity is observed as the spirolactam ring opens to give the highly fluorescent form of the molecule. The ligands are bimodal when coordinated to Tb(III) ions, inducing fluorescence from both the lanthanide center and the rhodamine fluorophore, on two independent time-frames. Confocal imaging experiments were carried out to establish the localization of Gd.L2 in HEK cells. Co-localisation with MitoTracker® Green confirmed that Gd.L2 compartmentalizes in the mitochondria. Gd.L2 was also evaluated as an MRI probe for imaging tumors in BALB/c nude mice bearing M21 xenografts. A 36.5% decrease in T1 within the tumor was observed 30 minutes post injection showing that Gd.L2 is preferentially up taken in the tumor. Gd.L2 is the first small molecule MR/fluorescent dual-modal imaging agent to display an off-on pH switch upon its preferential uptake within the more acidic micro-environment of tumor cells

    The impact of species and cell type on the nanosafety profile of iron oxide nanoparticles in neural cells

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    Background: While nanotechnology is advancing rapidly, nanosafety tends to lag behind since general mechanistic insights into cell-nanoparticle (NP) interactions remain rare. To tackle this issue, standardization of nanosafety assessment is imperative. In this regard, we believe that the cell type selection should not be overlooked since the applicability of cell lines could be questioned given their altered phenotype. Hence, we evaluated the impact of the cell type on in vitro nanosafety evaluations in a human and murine neuroblastoma cell line, neural progenitor cell line and in neural stem cells. Acute toxicity was evaluated for gold, silver and iron oxide (IO) NPs, and the latter were additionally subjected to a multiparametric analysis to assess sublethal effects. Results: The stem cells and murine neuroblastoma cell line respectively showed most and least acute cytotoxicity. Using high content imaging, we observed cell type-and species-specific responses to the IONPs on the level of reactive oxygen species production, calcium homeostasis, mitochondrial integrity and cell morphology, indicating that cellular homeostasis is impaired in distinct ways. Conclusions: Our data reveal cell type-specific toxicity profiles and demonstrate that a single cell line or toxicity end point will not provide sufficient information on in vitro nanosafety. We propose to identify a set of standard cell lines for screening purposes and to select cell types for detailed nanosafety studies based on the intended application and/or expected exposure

    Exploring the cellular accumulation of metal complexes

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    Transition metal complexes offer great potential as diagnostic and therapeutic agents, and a growing number of biological applications have been explored. To be effective, these complexes must reach their intended target inside the cell. Here we review the cellular accumulation of metal complexes, including their uptake, localization, and efflux. Metal complexes are taken up inside cells through various mechanisms, including passive diffusion and entry through organic and metal transporters. Emphasis is placed on the methods used to examine cellular accumulation, to identify the mechanism(s) of uptake, and to monitor possible efflux. Conjugation strategies that have been employed to improve the cellular uptake characteristics of metal complexes are also described
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