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Pharmaceuticals (Basel, Switzerland) Dec 2023[Ru(bipy)(dpphen)]Cl (where bipy = 2,2'-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline) (complex ) is a sterically strained compound that exhibits promising in...
A Ru(II)-Strained Complex with 2,9-Diphenyl-1,10-phenanthroline Ligand Induces Selective Photoactivatable Chemotherapeutic Activity on Human Alveolar Carcinoma Cells via Apoptosis.
[Ru(bipy)(dpphen)]Cl (where bipy = 2,2'-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline) (complex ) is a sterically strained compound that exhibits promising in vitro photocytotoxicity on an array of cell lines. Since lung adenocarcinoma cancer remains the most common lung cancer and the leading cause of cancer deaths, the current study aims to evaluate the plausible effect and uptake of complex on human alveolar carcinoma cells (A549) and mesenchymal stem cells (MSC), and assess its cytotoxicity in vitro while considering its effect on cell morphology, membrane integrity and DNA damage. MSC and A549 cells showed similar rates of complex uptake with a plateau at 12 h. Upon photoactivation, complex exhibited selective, potent anticancer activity against A549 cells with phototoxicity index (PI) values of 16, 25 and 39 at 24, 48 and 72 h, respectively. This effect was accompanied by a significant increase in A549-cell rounding and detachment, loss of membrane integrity and DNA damage. Flow cytometry experiments confirmed that A549 cells undergo apoptosis when treated with complex followed by photoactivation. In conclusion, this present study suggests that complex might be a promising candidate for photochemotherapy with photoproducts that possess selective anticancer effects in vitro. These results are encouraging to probe the potential activity of this complex in vivo.
PubMed: 38256884
DOI: 10.3390/ph17010050 -
Plants (Basel, Switzerland) Jan 2024For skin health promotion and cosmetic applications, combinations of plant cell extracts are extensively utilized. As most natural ingredient suppliers offer crude...
For skin health promotion and cosmetic applications, combinations of plant cell extracts are extensively utilized. As most natural ingredient suppliers offer crude extracts from individual plants or specific isolated compounds, the potential interactions between them are assessed in the development phase of cosmetic products. The industry seeks extract combinations that have undergone optimization and scrutiny for their bioactivities. This study presents a combination of two sustainably produced botanical ingredients and outlines their chemical composition, in vitro safety, and bioactivity for skin health enhancement. The amalgamation comprises the extract of processing waste and the extract from callus culture. Chemical analysis revealed distinct compounds within the extracts, and their combination led to a broader array of potentially synergistic compounds. In vitro assessments on skin cells demonstrated that the combination possesses robust antioxidant properties and the ability to stimulate keratinocyte proliferation, along with regulating collagen type I and matrix metalloproteinase 1 (MMP-1) production by dermal fibroblasts. The identified traits of this combination render it an appealing cosmetic component. To the best of our knowledge, this represents the first case when the extracts derived from medicinal plant processing waste and biotechnological plant cell cultivation processes have been combined and evaluated for their bioactivity.
PubMed: 38256840
DOI: 10.3390/plants13020287 -
International Journal of Molecular... Jan 2024Photodynamic therapy (PDT) is a two-stage treatment that implies the use of light energy, oxygen, and light-activated compounds (photosensitizers) to elicit cancerous... (Review)
Review
Photodynamic therapy (PDT) is a two-stage treatment that implies the use of light energy, oxygen, and light-activated compounds (photosensitizers) to elicit cancerous and precancerous cell death after light activation (phototoxicity). The biophysical, bioengineering aspects and its combinations with other strategies are highlighted in this review, both conceptually and as they are currently applied clinically. We further explore the recent advancements of PDT with the use of nanotechnology, including quantum dots as innovative photosensitizers or energy donors as well as the combination of PDT with radiotherapy and immunotherapy as future promising cancer treatments. Finally, we emphasize the potential significance of organoids as physiologically relevant models for PDT.
Topics: Photosensitizing Agents; Immunotherapy; Bioengineering; Biomedical Engineering; Photochemotherapy; Neoplasms
PubMed: 38256096
DOI: 10.3390/ijms25021023 -
Nature Methods Feb 2024The development of high-resolution microscopes has made it possible to investigate cellular processes in 3D and over time. However, observing fast cellular dynamics...
The development of high-resolution microscopes has made it possible to investigate cellular processes in 3D and over time. However, observing fast cellular dynamics remains challenging because of photobleaching and phototoxicity. Here we report the implementation of two content-aware frame interpolation (CAFI) deep learning networks, Zooming SlowMo and Depth-Aware Video Frame Interpolation, that are highly suited for accurately predicting images in between image pairs, therefore improving the temporal resolution of image series post-acquisition. We show that CAFI is capable of understanding the motion context of biological structures and can perform better than standard interpolation methods. We benchmark CAFI's performance on 12 different datasets, obtained from four different microscopy modalities, and demonstrate its capabilities for single-particle tracking and nuclear segmentation. CAFI potentially allows for reduced light exposure and phototoxicity on the sample for improved long-term live-cell imaging. The models and the training and testing data are available via the ZeroCostDL4Mic platform.
Topics: Deep Learning; Microscopy; Single Molecule Imaging; Motion
PubMed: 38238557
DOI: 10.1038/s41592-023-02138-w -
Photodiagnosis and Photodynamic Therapy Feb 2024Recent COVID crisis has demonstrated that modern society urgently needs an accessible protection against mass infections, especially viruses, as the new strains are...
BACKGROUND
Recent COVID crisis has demonstrated that modern society urgently needs an accessible protection against mass infections, especially viruses, as the new strains are appearing at an ever-increasing pace and cause severe harm to the population and the world economy.
METHODS
We have developed an efficient phthalocyanine photosensitizer LASU, that is suitable for dyeing textiles and allows to prepare reusable self-disinfecting fabrics with strong antiviral properties. The safety profile of LASU was evaluated in accredited laboratories by several in vitro assays according to the OECD-guidelines.
RESULTS
The textiles impregnated with LASU phthalocyanine showed a significant antiviral photodynamic effect even under moderate indoor and outdoor light. The dye did not show any genotoxic potential in human lymphocyte micronucleus assay. It showed a possible indication for eye irritation in human EpiOcular™ model and was phototoxic when tested in mouse BALB/c 3T3 cell test in the presence and absence of UVA-irradiation.
CONCLUSION
Novel phthalocyanine-dyed textiles are suitable for general use as self-disinfecting antiviral barriers and materials in hospitals, households, and public places. The safety profile of LASU is the phototoxic effect which is related to LASU´s mode of action.
Topics: Humans; Animals; Mice; Photosensitizing Agents; Photochemotherapy; Coloring Agents; Indoles; Antiviral Agents; Textiles; Isoindoles
PubMed: 38237650
DOI: 10.1016/j.pdpdt.2024.103978 -
BioRxiv : the Preprint Server For... Dec 2023Pain is comprised of a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This...
SIGNIFICANCE
Pain is comprised of a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes understanding pain particularly challenging as it involves rich interactions between many circuits (e.g., neural and vascular) and signaling cascades throughout the body. As such, experimentation on a single region may lead to an incomplete and potentially incorrect understanding of crucial underlying mechanisms.
AIM
Here, we aimed to develop and validate new tools to enable detailed and extended observation of neural and vascular activity in the brain and spinal cord. The first key set of innovations were targeted to developing novel imaging hardware that addresses the many challenges of multi-site imaging. The second key set of innovations were targeted to enabling bioluminescent imaging, as this approach can address limitations of fluorescent microscopy including photobleaching, phototoxicity and decreased resolution due to scattering of excitation signals.
APPROACH
We designed 3D-printed brain and spinal cord implants to enable effective surgical implantations and optical access with wearable miniscopes or an open window (e.g., for one- or two-photon microscopy or optogenetic stimulation). We also tested the viability for bioluminescent imaging, and developed a novel modified miniscope optimized for these signals (BLmini).
RESULTS
Here, we describe novel 'universal' implants for acute and chronic simultaneous brain-spinal cord imaging and optical stimulation. We further describe successful imaging of bioluminescent signals in both foci, and a new miniscope, the 'BLmini,' which has reduced weight, cost and form-factor relative to standard wearable miniscopes.
CONCLUSIONS
The combination of 3D printed implants, advanced imaging tools, and bioluminescence imaging techniques offers a new coalition of methods for understanding spinal cord-brain interactions. This work has the potential for use in future research into neuropathic pain and other sensory disorders and motor behavior.
PubMed: 38234789
DOI: 10.1101/2023.12.25.573323 -
Acta Naturae 2023Despite the significant potential of photodynamic therapy (PDT) as a minimally invasive treatment modality, the use of this method in oncology has remained limited due...
Despite the significant potential of photodynamic therapy (PDT) as a minimally invasive treatment modality, the use of this method in oncology has remained limited due to two serious problems: 1) limited penetration of the excitation light in tissues, which makes it impossible to affect deep-seated tumors and 2) use of chemical photosensitizers that slowly degrade in the body and cause photodermatoses and hyperthermia in patients. To solve these problems, we propose a fully biocompatible targeted system for PDT that does not require an external light source. The proposed system is based on bioluminescent resonance energy transfer (BRET) from the oxidized form of the luciferase substrate to the photosensitizing protein SOPP3. The BRET-activated system is composed of the multimodal protein DARP-NanoLuc-SOPP3, which contains a BRET pair NanoLuc-SOPP3 and a targeting module DARPin. The latter provides the interaction of the multimodal protein with tumors overexpressing tumor-associated antigen HER2 (human epidermal growth factor receptor type II). experiments in a 2D monolayer cell culture and a 3D spheroid model have confirmed HER2-specific photo-induced cytotoxicity of the system without the use of an external light source; in addition, experiments in animals with subcutaneous HER2-positive tumors have shown selective accumulation of DARP-NanoLuc-SOPP3 on the tumor site. The fully biocompatible system for targeted BRET-induced therapy proposed in this work makes it possible to overcome the following limitations: 1) the need to use an external light source and 2) the side phototoxic effect from aberrant accumulation of chemical photosensitizers. The obtained results demonstrate that the fully protein-based self-excited BRET system has a high potential for targeted PDT.
PubMed: 38234600
DOI: 10.32607/actanaturae.27331 -
Photodiagnosis and Photodynamic Therapy Feb 2024The induction of phototoxicity during photodynamic therapy (PDT) is dependent on oxygen availability. For this reason, the development of sensors to measure oxygen and...
BACKGROUND
The induction of phototoxicity during photodynamic therapy (PDT) is dependent on oxygen availability. For this reason, the development of sensors to measure oxygen and oxygen consumption is extremely important.
APPROACH
In this project we have used Fluorescence Lifetime imaging (FLIM) and Phosphorescence Lifetime Imaging/ delayed Fluorescence Lifetime Imaging (PLIM/dFLIM) to investigate the ability of bromine indirubin derivatives as oxygen sensors.
RESULTS
The oxygen sensitivity of bromine indirubins was detected through PLIM/dFLIM. Moreover, we have observed, by measuring nicotinamide adenine dinucleotide (NADH) FLIM, that bromine indirubin has a significant impact on cellular metabolism by shifting the SCC-4 Cells metabolism from oxidative phosphorylation (OXPHOS) to glycolysis.
CONCLUSIONS
In conclusion, this study successfully achieves its goals and provides important insights into the use of indirubin as a potential oxygen consumption sensor with the capability to identify and differentiate between normoxic and hypoxic regions within the cells.
Topics: Humans; Oxygen; Bromine; Photochemotherapy; Photosensitizing Agents; Hypoxia; Indoles
PubMed: 38218570
DOI: 10.1016/j.pdpdt.2024.103964 -
Journal of Biological Inorganic... Feb 2024Two novel cyclometallated iridium(III) complexes have been prepared with one bidentate or two monodentate imidazole-based ligands, 1 and 2, respectively. The complexes...
Phototoxicity of cyclometallated Ir(III) complexes bearing a thio-bis-benzimidazole ligand, and its monodentate analogue, as potential PDT photosensitisers in cancer cell killing.
Two novel cyclometallated iridium(III) complexes have been prepared with one bidentate or two monodentate imidazole-based ligands, 1 and 2, respectively. The complexes showed intense emission with long lifetimes of the excited state. Femtosecond transient absorption experiments established the nature of the lowest excited state as IL state. Singlet oxygen generation with good yields (40% for 1 and 82% for 2) was established by detecting O directly, through its emission at 1270 nm. Photostability studies were also performed to assess the viability of the complexes as photosensitizers (PS) for photodynamic therapy (PDT). Complex 1 was selected as a good candidate to investigate light-activated killing of cells, whilst complex 2 was found to be toxic in the dark and unstable under light. Complex 1 demonstrated high phototoxicity indexes (PI) in the visible region, PI > 250 after irradiation at 405 nm and PI > 150 at 455 nm, in EJ bladder cancer cells.
Topics: Ligands; Cell Line, Tumor; Photosensitizing Agents; Cell Death; Photochemotherapy; Iridium; Neoplasms; Benzimidazoles
PubMed: 38183420
DOI: 10.1007/s00775-023-02031-z -
Scientific Reports Dec 2023The ability of cells to move and migrate is required during development, but also in the adult in processes such as wound healing and immune responses. In addition,...
The ability of cells to move and migrate is required during development, but also in the adult in processes such as wound healing and immune responses. In addition, cancer cells exploit the cells' ability to migrate and invade to spread into nearby tissue and eventually metastasize. The majority of cancer deaths are caused by metastasis and the process of cell migration is therefore intensively studied. A common way to study cell migration is to observe cells through an optical microscope and record their movements over time. However, segmenting and tracking moving cells in phase contrast time-lapse video sequences is a challenging task. Several tools to track the velocity of migrating cells have been developed. Unfortunately, most of the automated tools are made for fluorescence images even though unlabelled cells are often preferred to avoid phototoxicity. Consequently, researchers are constrained with laborious manual tracking tools using ImageJ or similar software. We have therefore developed a freely available, user-friendly, automated tracking tool called CellTraxx. This software makes it easy to measure the velocity and directness of migrating cells in phase contrast images. Here, we demonstrate that our tool efficiently recognizes and tracks unlabelled cells of different morphologies and sizes (HeLa, RPE1, MDA-MB-231, HT1080, U2OS, PC-3) in several types of cell migration assays (random migration, wound healing and cells embedded in collagen). We also provide a detailed protocol and download instructions for CellTraxx.
Topics: Adult; Humans; Cell Movement; Software; HeLa Cells; Wound Healing; Cell Migration Assays; Cell Tracking; Image Processing, Computer-Assisted
PubMed: 38151514
DOI: 10.1038/s41598-023-50227-9