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Journal of Materials Chemistry. B Jun 2024An organelle-selective vision provides insights into the physiological response of plants and crops to environmental stresses in sustainable agriculture ecosystems....
An organelle-selective vision provides insights into the physiological response of plants and crops to environmental stresses in sustainable agriculture ecosystems. Biological applications often require two-photon excited fluorophores with low phototoxicity, high brightness, deep penetration, and tuneable cell entry. We obtained three aniline-based squaraines (SQs) tuned from hydrophobic to hydrophilic characteristics by modifying terminal pendant groups and substituents, and investigated their steady-state absorption and far-red-emitting fluorescence properties. The SQs exhibited two-photon absorption (2PA) ranging from 750 to 870 nm within the first biological spectral window; their structure-property relationships, corresponding to the 2PA cross sections (), and structure differences were demonstrated. The maximum value was ∼1220 GM at 800 nm for hydrophilic SQ3. Distinct biological staining efficiency and selective SQ bioimaging were evaluated utilizing the onion epidermal cell model. Contrary to the hydrophobic SQ1 results in the onion epidermal cell wall, amphiphilic SQ2 tagged the vacuole and nucleus and SQ3 tagged the vacuole. Distinguishable staining profiles in the roots and leaves were achieved. We believe that this study is the first to demonstrate distinct visualisation efficiency induced by the structure differences of two-photon excited SQs. Our results can help establish the versatile roles of novel near-infrared-emitting SQs in biological applications.
Topics: Structure-Activity Relationship; Aniline Compounds; Fluorescent Dyes; Onions; Phenols; Cyclobutanes; Photons; Molecular Structure; Optical Imaging; Plant Cells
PubMed: 38738315
DOI: 10.1039/d4tb00400k -
European Journal of Medicinal Chemistry Jun 2024Small molecule photosensitizers for combined in vivo tailored cancer diagnostics and photodynamic/photothermal therapy are desperately needed. Monoamine oxidase A...
Small molecule photosensitizers for combined in vivo tailored cancer diagnostics and photodynamic/photothermal therapy are desperately needed. Monoamine oxidase A (MAO-A)-activated therapeutic and diagnostic compounds provide great selectivity because MAO-A can be employed as a biomarker for associated Tumors. In order to screen photosensitizers with photodynamic therapeutic potential, we have created a range of near-infrared fluorescent molecules in this work by combining dihydroxanthene parent with various heterocyclic fluorescent dyes. The NIR fluorescent diagnostic probe, DHMQ, was created by combining the screened fluorescent dye matrices with the propylamino group, which is the recognition moiety of MAO-A, based on the oxidative deamination mechanism of the enzyme. This probe has a low toxicity level and can identify MAO-A precisely. It has the ability to use fluorescence imaging on mice and cells to track MAO-A activity in real-time. It has strong phototoxicity and can produce singlet oxygen when exposed to laser light. The temperature used in photothermal imaging can get up to 50 °C, which can harm tumor cells permanently and have a positive phototherapeutic impact on tumors grown from SH-SY5Y xenograft mice. The concept of using MAO-A effectively in diseases is expanded by the MAO-A-activated diagnostic-integrated photosensitizers, which offer a new platform for in vivo cancer diagnostics and targeted anticancer treatment.
Topics: Photosensitizing Agents; Animals; Humans; Monoamine Oxidase; Photochemotherapy; Mice; Photothermal Therapy; Xanthenes; Molecular Structure; Antineoplastic Agents; Structure-Activity Relationship; Fluorescent Dyes; Cell Proliferation; Cell Line, Tumor; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Mice, Nude
PubMed: 38735149
DOI: 10.1016/j.ejmech.2024.116474 -
Water Research Jun 2024Photochemical processes are typically not incorporated in screening-level substance risk assessments due to the complexity of modeling sunlight co-exposures and...
Direct and indirect photodegradation in aquatic systems mitigates photosensitized toxicity in screening-level substance risk assessments of selected petrochemical structures.
Photochemical processes are typically not incorporated in screening-level substance risk assessments due to the complexity of modeling sunlight co-exposures and resulting interactions on environmental fate and effects. However, for many substances, sunlight exerts a profound influence on environmental degradation rates and ecotoxicities. Recent modeling advances provide an improved technical basis for estimating the effect of sunlight in modulating both substance exposure and toxicity in the aquatic environment. Screening model simulations were performed for 25 petrochemical structures with varied uses and environmental fate properties. Model predictions were evaluated by comparing the ratios of predicted exposure concentrations with and without light to the corresponding ratios of toxicity thresholds under the same conditions. The relative ratios of exposure and hazard in light vs. dark were then used to evaluate how inclusion of light modulates substance risk analysis. Results indicated that inclusion of light reduced PECs by factors ranging from 1.1- to 63-fold as a result of photodegradation, while reducing PNECs by factors ranging from 1- to 49-fold due to photoenhanced toxicity caused by photosensitization. Consequently, the presence of light altered risk quotients by factors that ranged from 0.1- to 17-fold, since the predicted increase in substance hazard was mitigated by the reduction in exposure. For many structures, indirect photodegradation decreases environmental exposures independently of the direct photolysis pathway which is associated with enhanced phototoxicity. For most of the scenarios and chemicals in the present work, photosensitization appears to be mitigated by direct and indirect degradation from sunlight exposure.
Topics: Risk Assessment; Photolysis; Water Pollutants, Chemical; Sunlight; Models, Theoretical
PubMed: 38728777
DOI: 10.1016/j.watres.2024.121677 -
Inorganic Chemistry May 2024A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-][1,10]phenanthroline...
A series of Ru(II) complexes incorporating two 4,4'-bis(trifluoromethyl)-2,2'-bipyridine (4,4'-btfmb) coligands and thienyl-appended imidazo[4,5-][1,10]phenanthroline (IP-T) ligands was characterized and assessed for phototherapy effects toward cancer cells. The [Ru(4,4'-btfmb)(IP-T)] scaffold has greater overall redox activity compared to Ru(II) polypyridyl complexes such as [Ru(bpy)]. - have additional oxidations due to the T group and additional reductions due to the 4,4'-btfmb ligands. - also exhibit T-based reductions. exhibits two oxidations and eight reductions within the potential window of -3 to +1.5 V. The lowest-lying triplets (T) for - are metal-to-ligand charge-transfer (MLCT) excited states with lifetimes around 1 μs, whereas T for - is longer-lived (∼20-24 μs) and of significant intraligand charge-transfer (ILCT) character. Phototoxicity toward melanoma cells (SK-MEL-28) increases with , with having a visible EC value as low as 9 nM and PI as large as 12,000. and retain some of this activity in hypoxia, where has a visible EC as low as 35 nM and PI as high as 2900. Activity over six biological replicates is consistent and within an order of magnitude. These results demonstrate the importance of lowest-lying ILCT states for phototoxicity and maintaining activity in hypoxia.
PubMed: 38728376
DOI: 10.1021/acs.inorgchem.3c04382 -
Journal of Medicinal Chemistry May 2024Migration of immune cells to sites of inflammation is a critical step in the body's response to infections but also during autoimmune flares. Chemokine receptors,...
Migration of immune cells to sites of inflammation is a critical step in the body's response to infections but also during autoimmune flares. Chemokine receptors, members of the GPCR receptors, are instrumental in directing specific cell types to their target organs. Herein, we describe a highly potent small molecule antagonist of the chemokine receptor CCR6, which came out of fine-tuned structural elaborations from a proprietary HTS hit. Three main issues in the parent chemical series-cytotoxicity, phototoxicity, and hERG, were successfully solved. Biological characterization demonstrated that compound (IDOR-1117-2520) is a selective and insurmountable antagonist of CCR6. In vivo proof-of-mechanism studies in a mouse lung inflammation model using a representative compound from the chemical class of confirmed that the targeted CCR6 cells were efficiently inhibited from migrating into the bronchoalveoli. Finally, ADMET and physicochemical properties were well balanced and the preclinical package warranted progress in the clinic.
Topics: Receptors, CCR6; Animals; Humans; Autoimmune Diseases; Mice; Structure-Activity Relationship; Drug Discovery
PubMed: 38727100
DOI: 10.1021/acs.jmedchem.4c00186 -
Neurophotonics Apr 2024Pain comprises a complex interaction between motor action and somatosensation that is dependent on dynamic interactions between the brain and spinal cord. This makes...
SIGNIFICANCE
Pain comprises 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
We aimed to develop and validate tools to enable detailed and extended observation of neural and vascular activity in the brain and spinal cord. The first key set of innovations was targeted to developing novel imaging hardware that addresses the many challenges of multisite imaging. The second key set of innovations was targeted to enabling bioluminescent (BL) 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 BL imaging and developed a novel modified miniscope optimized for these signals (BLmini).
RESULTS
We describe "universal" implants for acute and chronic simultaneous brain-spinal cord imaging and optical stimulation. We further describe successful imaging of BL 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 coalition of methods for understanding spinal cord-brain interactions. Our work has the potential for use in future research into neuropathic pain and other sensory disorders and motor behavior.
PubMed: 38725801
DOI: 10.1117/1.NPh.11.2.024209 -
Toxicology in Vitro : An International... Jun 2024Vitamin K possesses efficacy as a topical dermatological agent. However, vitamin K is phototoxic and susceptible to photodegradation. Herein, we investigated the...
Vitamin K possesses efficacy as a topical dermatological agent. However, vitamin K is phototoxic and susceptible to photodegradation. Herein, we investigated the mechanisms underlying the phototoxicity of phylloquinone (PK, vitamin K) and menaquinone-4 (MK-4, vitamin K) under ultraviolet A (UVA) irradiation using various reactive oxygen species (ROS) scavengers. This resulted in the production of superoxide anion radicals via type I and singlet oxygen via type II photodynamic reactions, which were quenched by the ROS scavengers: superoxide dismutase and sodium azide (NaN). In HaCaT cells, MK-4 and PK induced the production of intracellular ROS, particularly hydrogen peroxide, in response to UVA irradiation. Furthermore, the addition of catalase successfully decreased maximum ROS levels by approximately 30%. NaN and catalase decreased the maximum reduction in cell viability induced by UVA-irradiated PK and MK-4 in cell viability by approximately 2-7-fold. Additionally, ROS scavengers had no effect on the photodegradation of PK or MK-4 at 373 nm. Therefore, the phototoxicities of PK and MK-4 were attributed to the generation of singlet oxygen and hydrogen peroxide, underscoring the importance of photoshielding in circumventing phototoxicity.
Topics: Ultraviolet Rays; Reactive Oxygen Species; Humans; Free Radical Scavengers; Cell Survival; Sodium Azide; Cell Line; Vitamin K 2; Vitamin K 1; Dermatitis, Phototoxic; Catalase; HaCaT Cells; Superoxide Dismutase
PubMed: 38723978
DOI: 10.1016/j.tiv.2024.105839 -
Journal of Photochemistry and... Jul 2024Emerging antibiotic resistance among bacterial pathogens has forced an urgent need for alternative non-antibiotic strategies development that could combat drug...
INTRODUCTION
Emerging antibiotic resistance among bacterial pathogens has forced an urgent need for alternative non-antibiotic strategies development that could combat drug resistant-associated infections. Suppression of virulence of ESKAPE pathogens' by targeting multiple virulence traits provides a promising approach.
OBJECTIVES
Here we propose an iron-blocking antibacterial therapy based on a cationic heme-mimetic gallium porphyrin (GaCHP), which antibacterial efficacy could be further enhanced by photodynamic inactivation.
METHODS
We used gallium heme mimetic porphyrin (GaCHP) excited with light to significantly reduce microbial viability and suppress both the expression and biological activity of several virulence traits of both Gram-positive and Gram-negative ESKAPE representatives, i.e., S. aureus and P. aeruginosa. Moreover, further improvement of the proposed strategy by combining it with routinely used antimicrobials to resensitize the microbes to antibiotics and provide enhanced bactericidal efficacy was investigated.
RESULTS
The proposed strategy led to substantial inactivation of critical priority pathogens and has been evidenced to suppress the expression and biological activity of multiple virulence factors in S. aureus and P. aeruginosa. Finally, the combination of GaCHP phototreatment and antibiotics resulted in promising strategy to overcome antibiotic resistance of the studied microbes and to enhance disinfection of drug resistant pathogens.
CONCLUSION
Lastly, considering high safety aspects of the proposed treatment toward host cells, i.e., lack of mutagenicity, no dark toxicity and mild phototoxicity, we describe an efficient alternative that simultaneously suppresses the functionality of multiple virulence factors in ESKAPE pathogens.
Topics: Photosensitizing Agents; Gallium; Porphyrins; Pseudomonas aeruginosa; Staphylococcus aureus; Heme; Anti-Bacterial Agents; Virulence; Microbial Sensitivity Tests; Light; Drug Resistance, Bacterial
PubMed: 38723545
DOI: 10.1016/j.jphotobiol.2024.112928 -
Journal of Fluorescence May 2024Due to the unique chemical and biomedical properties of carbon dots (CDs), they have increasingly obtained the attention in many research fields, for example,...
Due to the unique chemical and biomedical properties of carbon dots (CDs), they have increasingly obtained the attention in many research fields, for example, bioimaging, fluorescence sensing, and drug delivery, etc. Recently, it was found that, under light excitation, CDs can also be exploited as a novel photosensitizer to prepare reactive oxygen species (ROS), which expand their applications in the field of photodynamic therapy for cancer treatment. Nevertheless, the high cost and complex fabrication approach of CDs significantly limit their applications. To address this issue, bottom-up routes usually utilize sustainable and inexpensive carbon precursor as starting materials, employed N,N-dimethylformamide (DMF) or ethanol as an environmental-friendly solvent. Bottom-up approach was energy efficient, and the purification process was relatively simple by dialysis. Therefore, carbon dots (CDs) were facilely fabricated in a one-pot solvothermal process using 1-aminoanthraquinone as a precursor, and their application as photosensitizers for in vitro antitumor cells, especially photodynamic therapy (PDT) was established. Then the photophysical and nanoscale dimensions properties of the fabricated CDs were characterized via TEM, UV-visible, fluorescence, and FT-IR spectroscopy. The synthesized N-doped CDs can easily dissolve in water, possess very low biotoxicity, yellow-light emission (maximum peak at 587 nm). More importantly, PDT studies demonstrated that the obtained CDs possess a high singlet oxygen yield of 35%, and exhibit significant phototoxicity to cancer cells upon 635 nm laser irradiation. These studies highlight that N-doped CDs can be facilely synthesized from only one precursor, and are a potentially novel theranostic agent for in vivo PDT.
PubMed: 38717650
DOI: 10.1007/s10895-024-03725-6