scholarly journals Red Light-Emitting Water-Soluble Luminescent Iridium-Containing Polynorbornenes: Synthesis, Characterization and Oxygen Sensing Properties in Biological Tissues in Vivo

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6349
Author(s):  
Leonid N. Bochkarev ◽  
Yulia P. Parshina ◽  
Yana V. Gracheva ◽  
Tatyana A. Kovylina ◽  
Svetlana A. Lermontova ◽  
...  
Keyword(s):  
Normal Skin ◽  
Red Light ◽  
Biological Tissues ◽  
Water Soluble ◽  
Quantum Yields ◽  
Preliminary Evaluation ◽  
Iridium Complexes ◽  
Phosphorescence Lifetime ◽  
Biological Studies

New water-soluble polynorbornenes P1–P4 containing oligoether, amino acid groups and luminophoric complexes of iridium(III) were synthesized by ring-opening metathesis polymerization. The polymeric products in organic solvents and in water demonstrate intense photoluminescence in the red spectral region. The polymers P1 and P3 with 1-phenylisoquinoline cyclometalating ligands in iridium fragments reveal 4–6 fold higher emission quantum yields in solutions than those of P2 and P4 that contain iridium complexes with 1-(thien-2-yl)isoquinoline cyclometalating ligands. The emission parameters of P1–P4 in degassed solutions essentially differ from those in the aerated solutions showing oxygen-dependent quenching of phosphorescence. Biological testing of P1 and P3 demonstrates that the polymers do not penetrate into live cultured cancer cells and normal skin fibroblasts and do not possess cytotoxicity within the concentrations and time ranges reasonable for biological studies. In vivo, the polymers display longer phosphorescence lifetimes in mouse tumors than in muscle, as measured using phosphorescence lifetime imaging (PLIM), which correlates with tumor hypoxia. Therefore, preliminary evaluation of the synthesized polymers shows their suitability for noninvasive in vivo assessments of oxygen levels in biological tissues.

scholarly journals Water-soluble cyclometalated platinum(ii) and iridium(iii) complexes: synthesis, tuning of the photophysical properties, and in vitro and in vivo phosphorescence lifetime imaging

RSC Advances ◽  
2018 ◽  
Vol 8 (31) ◽  
pp. 17224-17236 ◽  
Author(s):  
Anastasia I. Solomatina ◽  
Shih-Hao Su ◽  
Maria M. Lukina ◽  
Varvara V. Dudenkova ◽  
Vladislav I. Shcheslavskiy ◽  
...  
Keyword(s):  
Photophysical Properties ◽  
Water Soluble ◽  
Iridium Complexes ◽  
Hypoxia Imaging ◽  
Phosphorescence Lifetime ◽  
Lifetime Imaging ◽  
Phosphorescence Lifetime Imaging

Novel water-soluble iridium complexes with sulfonated diphosphine allow in vitro and in vivo lifetime hypoxia imaging.

scholarly journals Preparation, Cytotoxicity, and In Vitro Bioimaging of Water Soluble and Highly Fluorescent Palladium Nanoclusters

2020 ◽  
Vol 7 (1) ◽  
pp. 20 ◽  
Author(s):  
Suresh Thangudu ◽  
Poliraju Kalluru ◽  
Raviraj Vankayala
Keyword(s):  
In Vitro Cytotoxicity ◽  
Molecular Probes ◽  
Water Soluble ◽  
Quantum Yields ◽  
Cell Labelling ◽  
Metal Nanoclusters ◽  
Extinction Coefficients ◽  
Cytotoxicity Studies

Fluorescent probes offer great potential to identify and treat surgical tumors by clinicians. To this end, several molecular probes were examined as in vitro and in vivo bioimaging probes. However, due to their ultra-low extinction coefficients as well as photobleaching problems, conventional molecular probes limit its practical utility. To address the above mentioned challenges, metal nanoclusters (MNCs) can serve as an excellent alternative with many unique features such as higher molar extinction coefficients/light absorbing capabilities, good photostability and appreciable fluorescence quantum yields. Herein, we reported a green synthesis of water soluble palladium nanoclusters (Pd NCs) and characterized them by using various spectroscopic and microscopic characterization techniques. These nanoclusters showed excellent photophysical properties with the characteristic emission peak centered at 500 nm under 420 nm photoexcitation wavelength. In vitro cytotoxicity studies in human cervical cancer cells (HeLa) cells reveal that Pd NCs exhibited good biocompatibility with an IC50 value of >100 µg/mL and also showed excellent co-localization and distribution throughout the cytoplasm region with a significant fraction translocating into cell nucleus. We foresee that Pd NCs will carry huge potential to serve as a new generation bioimaging nanoprobe owing to its smaller size, minimal cytotoxicity, nucleus translocation capability and good cell labelling properties.

scholarly journals Red Light Optogenetics in Neuroscience

2022 ◽  
Vol 15 ◽  
Author(s):  
Kimmo Lehtinen ◽  
Miriam S. Nokia ◽  
Heikki Takala
Keyword(s):  
Red Light ◽  
Long Term Potentiation ◽  
Biological Tissues ◽  
Infrared Light ◽  
Cellular Functions ◽  
Spatiotemporal Resolution ◽  
New Developments ◽  
Term Potentiation

Optogenetics, a field concentrating on controlling cellular functions by means of light-activated proteins, has shown tremendous potential in neuroscience. It possesses superior spatiotemporal resolution compared to the surgical, electrical, and pharmacological methods traditionally used in studying brain function. A multitude of optogenetic tools for neuroscience have been created that, for example, enable the control of action potential generation via light-activated ion channels. Other optogenetic proteins have been used in the brain, for example, to control long-term potentiation or to ablate specific subtypes of neurons. In in vivo applications, however, the majority of optogenetic tools are operated with blue, green, or yellow light, which all have limited penetration in biological tissues compared to red light and especially infrared light. This difference is significant, especially considering the size of the rodent brain, a major research model in neuroscience. Our review will focus on the utilization of red light-operated optogenetic tools in neuroscience. We first outline the advantages of red light for in vivo studies. Then we provide a brief overview of the red light-activated optogenetic proteins and systems with a focus on new developments in the field. Finally, we will highlight different tools and applications, which further facilitate the use of red light optogenetics in neuroscience.

Singlet Oxygen Release and Cell Toxicity of a Chemiluminescent Squaraine Rotaxane Dye: Implications for Molecular Imaging

2011 ◽  
Vol 64 (5) ◽  
pp. 604 ◽  
Author(s):  
Jung-Jae Lee ◽  
Amanda Gonçalves ◽  
Bryan A. Smith ◽  
Rachel Palumbo ◽  
Alexander G. White ◽  
...  
Keyword(s):  
Molecular Imaging ◽  
Singlet Oxygen ◽  
Cell Cultures ◽  
Near Infrared ◽  
Red Light ◽  
Infrared Emission ◽  
Water Soluble ◽  
Cell Toxicity ◽  
Squaraine Rotaxane

The water soluble tetraguanidinium squaraine rotaxane 2 was prepared and photoconverted to its corresponding squaraine rotaxane endoperoxide (SREP), 2EP. As expected, 2EP undergoes a thermal cycloreversion reaction that releases 60 ± 4% singlet oxygen and produces near-infrared emission in aqueous solution. Cell toxicity assays in the dark, using human and bacterial cell cultures, showed that 2EP (up to 20 µM) is no more toxic than its parent 2. This suggests that SREP-derived imaging probes are not likely to exhibit a significant toxicity effect due to the slow release of stoichiometric amounts of singlet oxygen. Additional photosensitization experiments showed that tetraguanidinium squaraine rotaxane 2 is a weak photosensitizer, but nonetheless, red light irradiation of cell cultures that were pre-incubated with 2 (>3 µM) produced moderate phototoxicity. Fluorescence microscopy studies attribute the phototoxicity of 2 to its ability to penetrate into the cell cytosol. The implications of these results are discussed in the context of effective methods to activate SREP as chemiluminescent probes for in vivo optical molecular imaging.

scholarly journals pH-Responsive N^C-Cyclometalated Iridium(III) Complexes: Synthesis, Photophysical Properties, Computational Results, and Bioimaging Application

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 232
Author(s):  
Anastasia Solomatina ◽  
Daria Kozina ◽  
Vitaly Porsev ◽  
Sergey Tunik
Keyword(s):  
Density Functional Theory ◽  
Excited State ◽  
Density Functional ◽  
Photophysical Properties ◽  
Picolinic Acid ◽  
State Density ◽  
Quantum Yields ◽  
Iridium Complexes ◽  
Functional Theory ◽  
Phosphorescence Lifetime

Herein we report four [Ir(N^C)2(L^L)]n+, n = 0,1 complexes (1–4) containing cyclometallated N^C ligand (N^CH = 1-phenyl-2-(4-(pyridin-2-yl)phenyl)-1H-phenanthro[9,10-d]imidazole) and various bidentate L^L ligands (picolinic acid (1), 2,2′-bipyridine (2), [2,2′-bipyridine]-4,4′-dicarboxylic acid (3), and sodium 4,4′,4″,4‴-(1,2-phenylenebis(phosphanetriyl))tetrabenzenesulfonate (4). The N^CH ligand precursor and iridium complexes 1–4 were synthesized in good yield and characterized using chemical analysis, ESI mass spectrometry, and NMR spectroscopy. The solid-state structure of 2 was also determined by XRD analysis. The complexes display moderate to strong phosphorescence in the 550–670 nm range with the quantum yields up to 30% and lifetimes of the excited state up to 60 µs in deoxygenated solution. Emission properties of 1–4 and N^CH are strongly pH-dependent to give considerable variations in excitation and emission profiles accompanied by changes in emission efficiency and dynamics of the excited state. Density functional theory (DFT) and time-dependent density functional theory (TD DFT) calculations made it possible to assign the nature of emissive excited states in both deprotonated and protonated forms of these molecules. The complexes 3 and 4 internalize into living CHO-K1 cells, localize in cytoplasmic vesicles, primarily in lysosomes and acidified endosomes, and demonstrate relatively low toxicity, showing more than 80% cells viability up to the concentration of 10 µM after 24 h incubation. Phosphorescence lifetime imaging microscopy (PLIM) experiments in these cells display lifetime distribution, the conversion of which into pH values using calibration curves gives the magnitudes of this parameter compatible with the physiologically relevant interval of the cell compartments pH.

Fenofibrate Solid Dispersion for Improving Oral Bioavailability: Preparation, and Characterization and in vivo Evaluation

2020 ◽  
Vol 13 (5) ◽  
pp. 5102-5109
Author(s):  
Venu Madhav K ◽  
Somnath De ◽  
Chandra Shekar Bonagiri ◽  
Sridhar Babu Gummadi
Keyword(s):  
Oral Bioavailability ◽  
Oral Delivery ◽  
Solid Dispersions ◽  
In Vitro Release ◽  
Aqueous Solubility ◽  
Water Soluble ◽  
Scanning Calorimetry ◽  
In Vivo Evaluation

Fenofibrate (FN) is used in the treatment of hypercholesterolemia. It shows poor dissolution and poor oral bioavailability after oral administration due to high liphophilicity and low aqueous solubility. Hence, solid dispersions (SDs) of FN (FN-SDs) were develop that might enhance the dissolution and subsequently oral bioavailability. FN-SDs were prepared by solvent casting method using different carriers (PEG 4000, PEG 6000, β cyclodextrin and HP β cyclodextrin) in different proportions (0.25%, 0.5%, 0.75% and 1% w/v). FN-SDs were evaluated solubility, assay and in vitro release studies for the optimization of SD formulation. Differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) analysis was performed for crystalline and morphology analysis, respectively. Further, optimized FN-SD formulation evaluated for pharmacokinetic performance in Wistar rats, in vivo in comparison with FN suspension.  From the results, FN-SD3 and FN-SD6 have showed 102.9 ±1.3% and 105.5±3.1% drug release, respectively in 2 h. DSC and PXRD studies revealed that conversion of crystalline to amorphous nature of FN from FT-SD formulation. SEM studies revealed the change in the orientation of FN when incorporated in SDs. The oral bioavailability FN-SD3 and FN-SD6 formulations exhibited 2.5-folds and 3.1-folds improvement when compared to FN suspension as control. Overall, SD of FN could be considered as an alternative dosage form for the enhancement of oral delivery of poorly water-soluble FN.

Chemosensitizing Activity of Histone Deacetylases Inhibitory Cyclic Hydroxamic Acids for Combination Chemotherapy of Lymphatic Leukemia

2018 ◽  
Vol 18 (4) ◽  
pp. 365-371 ◽  
Author(s):  
Denis V. Mishchenko ◽  
Margarita E. Neganova ◽  
Elena N. Klimanova ◽  
Tatyana E. Sashenkova ◽  
Sergey G. Klochkov ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Acute Toxicity ◽  
Histone Deacetylases ◽  
Hydroxamic Acids ◽  
Water Soluble ◽  
Male Rat ◽  
Hybrid Male ◽  
Cyclic Hydroxamic Acids

Background: Anti-tumor effect of hydroxamic acid derivatives is largely connected with its properties as efficient inhibitors of histone deacetylases, and other metalloenzymes involved in carcinogenesis. Objective: The work was aimed to (i) determine the anti-tumor and chemosensitizing activity of the novel racemic spirocyclic hydroxamic acids using experimental drug sensitive leukemia P388 of mice, and (ii) determine the structure-activity relationships as metal chelating and HDAC inhibitory agents. Method: Outbreed male rat of 200-220 g weights were used in biochemical experiments. In vivo experiments were performed using the BDF1 hybrid male mice of 22-24 g weight. Lipid peroxidation, Fe (II) -chelating activity, HDAC fluorescent activity, anti-tumor and anti-metastatic activity, acute toxicity techniques were used in this study. Results: Chemosensitizing properties of water soluble cyclic hydroxamic acids (CHA) are evaluated using in vitro activities and in vivo methods and found significant results. These compounds possess iron (II) chelating properties, and slightly inhibit lipid peroxidation. CHA prepared from triacetonamine (1a-e) are more effective Fe (II) ions cheaters, as compared to CHA prepared from 1- methylpiperidone (2a-e). The histone deacetylase (HDAC) inhibitory activity, lipophilicity and acute toxicity were influenced by the length amino acids (size) (Glycine < Alanine < Valine < Leucine < Phenylalanine). All compounds bearing spiro-N-methylpiperidine ring (2a-e) are non-toxic up to 1250 mg/kg dose, while compounds bearing spiro-tetramethylpiperidine ring (1a-e) exhibit moderate toxicity which increases with increasing lipophility, but not excite at 400 mg/kg. Conclusion: It was shown that the use of combination of non-toxic doses of cisplatin (cPt) or cyclophosphamide with CHA in most cases result in the appearance of a considerable anti-tumor effect of cytostatics. The highest chemosensitizing activity with respect to leukemia Р388 is demonstrated by the CHA derivatives of Valine 1c or 2c.

Assessment of Ploy Dopamine Coated Fe3O4 Nanoparticles for Melanoma (B16-F10 and A-375) Cells Detection

2020 ◽  
Vol 20 (16) ◽  
pp. 1918-1926
Author(s):  
Fahimeh H. Beigi ◽  
Soheil Fatahian ◽  
Sogand Shahbazi-Gahrouei ◽  
Daryoush Shahbazi-Gahrouei ◽  
Amin Farzadniya
Keyword(s):  
Mr Imaging ◽  
Mtt Assay ◽  
Fe3o4 Nanoparticles ◽  
Normal Skin ◽  
Iron Concentration ◽  
Positive Effects ◽  
Skin Cells ◽  
Melanoma B16 ◽  
Co Precipitation

Objective: Polydopamine coated iron oxide nanoparticles (Fe3O4@PDA NPs) were synthesized, characterized, and their MR imaging contrast agents and photothermal potency were evaluated on melanoma (B16-F10 and A-375) cells and normal skin cells. To this end, MTT assay, Fe concentration, and MR imaging of both coated and uncoated NPs were assessed in C57BL/6 mice. Methods: Fe3O4 nanoparticles were synthesized using co-precipitation, and coated with polydopamine. The cytotoxicity of Fe3O4 and Fe3O4@PDA NPs on melanoma cells, with different concentrations, were obtained using MTT assay. MR images and Fe concentrations of nanoprobe and nanoparticles were evaluated under in vivo conditions. Results: Findings indicated that uncoated Fe3O4 showed the highest toxicity in animal (B16-F10) cells at 450μg/ml after 72h, while the highest toxicity in human (A-375) cells were observed at 350μg/ml. These nanoparticles did not reveal any cytotoxicity to normal skin cells, despite having some toxicity features in A-375 cells. MR image signals in the tumor were low compared with other tissues. The iron concentration in the tumor was higher than that of other organs. Conclusion: It is concluded that the cytotoxicity of Fe3O4@PDA was found to be significantly lower than uncoated nanoparticles (p <0.001), which allows some positive effects on reducing toxicity. The prepared nanoprobe may be used as a contrast agent in MR imaging.

scholarly journals Development, Characterization and In Vivo Pharmacokinetic Assessment of Rectal Suppositories Containing Combination Antiretroviral Drugs for HIV Prevention

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1110
Author(s):  
Kunal Jhunjhunwala ◽  
Charles W. Dobard ◽  
Sunita Sharma ◽  
Natalia Makarova ◽  
Angela Holder ◽  
...  
Keyword(s):  
Hiv Prevention ◽  
Antiretroviral Drugs ◽  
Water Soluble ◽  
Fixed Dose ◽  
Receptive Anal Intercourse ◽  
On Demand ◽  
Dose Combination ◽  
Rectal Suppositories

Receptive anal intercourse (RAI) contributes significantly to HIV acquisition underscoring the need to develop HIV prevention options for populations engaging in RAI practices. We explored the feasibility of formulating rectal suppositories with potent antiviral drugs for on-demand use. A fixed-dose combination of tenofovir (TFV) and elvitegravir (EVG) (40 mg each) was co-formulated in six different suppository bases (three fat- and three water-soluble). Fat-soluble witepsol H15 and water-soluble polyethylene glycol (PEG) based suppositories demonstrated favorable in vitro release and were advanced to assess in vivo pharmacokinetics following rectal administration in macaques. In vivo drug release profiles were similar for both suppository bases. Median concentrations of TFV and EVG detected in rectal fluids at 2 h were 1- and 2-logs higher than the in vitro IC50, respectively; TFV-diphosphate levels in rectal tissues met or exceeded those associated with high efficacy against rectal simian HIV (SHIV) exposure in macaques. Leveraging on these findings, a PEG-based suppository with a lower dose combination of tenofovir alafenamide (TAF) and EVG (8 mg each) was developed and found to achieve similar rectal drug exposures in macaques. This study establishes the utility of rectal suppositories as a promising on-demand strategy for HIV PrEP and supports their clinical development.

scholarly journals Fibrillar pharmacology of functionalized nanocellulose

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sam Wong ◽  
Simone Alidori ◽  
Barbara P. Mello ◽  
Bryan Aristega Almeida ◽  
David Ulmert ◽  
...  
Keyword(s):  
Aspect Ratio ◽  
Fluorescent Dyes ◽  
Pharmacokinetic Profile ◽  
Water Soluble ◽  
Size Exclusion ◽  
Hydroxyl Groups ◽  
Target Tissue ◽  
Exclusion Chromatography ◽  
Specific Accumulation

AbstractCellulose nanocrystals (CNC) are linear organic nanomaterials derived from an abundant naturally occurring biopolymer resource. Strategic modification of the primary and secondary hydroxyl groups on the CNC introduces amine and iodine group substitution, respectively. The amine groups (0.285 mmol of amine per gram of functionalized CNC (fCNC)) are further reacted with radiometal loaded-chelates or fluorescent dyes as tracers to evaluate the pharmacokinetic profile of the fCNC in vivo. In this way, these nanoscale macromolecules can be covalently functionalized and yield water-soluble and biocompatible fibrillar nanoplatforms for gene, drug and radionuclide delivery in vivo. Transmission electron microscopy of fCNC reveals a length of 162.4 ± 16.3 nm, diameter of 11.2 ± 1.52 nm and aspect ratio of 16.4 ± 1.94 per particle (mean ± SEM) and is confirmed using atomic force microscopy. Size exclusion chromatography of macromolecular fCNC describes a fibrillar molecular behavior as evidenced by retention times typical of late eluting small molecules and functionalized carbon nanotubes. In vivo, greater than 50% of intravenously injected radiolabeled fCNC is excreted in the urine within 1 h post administration and is consistent with the pharmacological profile observed for other rigid, high aspect ratio macromolecules. Tissue distribution of fCNC shows accumulation in kidneys, liver, and spleen (14.6 ± 6.0; 6.1 ± 2.6; and 7.7 ± 1.4% of the injected activity per gram of tissue, respectively) at 72 h post-administration. Confocal fluorescence microscopy reveals cell-specific accumulation in these target tissue sinks. In summary, our findings suggest that functionalized nanocellulose can be used as a potential drug delivery platform for the kidneys.

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