The rapid evolution and spread of multidrug resistance among bacterial pathogens has significantly outpaced the development of new antibiotics, underscoring the urgent need for alternative therapies. Antimicrobial photodynamic therapy and antimicrobial sonodynamic therapy have emerged as promising treatments. Antimicrobial photodynamic therapy relies on the interaction between light and a photosensitizer to produce reactive oxygen species, which are highly cytotoxic to microorganisms, leading to their destruction without fostering resistance. Antimicrobial sonodynamic therapy, a novel variation, substitutes ultrasound for light to activate the sonosensitizers, expanding the therapeutic reach. To increase the efficiency of antimicrobial photodynamic therapy and antimicrobial sonodynamic therapy, the combination of these two methods, known as antimicrobial photo-sonodynamic therapy, is currently being explored and considered a promising approach. Recent advances, particularly in the application of nanomaterials, have further enhanced the efficacy of these therapies. Nanosensitizers, due to their improved reactive oxygen species generation and targeted delivery, offer significant advantages in overcoming the limitations of conventional sensitizers. These breakthroughs provide new avenues for treating bacterial infections, especially multidrug-resistant strains and biofilm-associated infections. Continued research, including comprehensive clinical studies, is crucial to optimizing nanomaterial-based antimicrobial photo-sonodynamic therapy for clinical use, ensuring their effectiveness in real-world applications.
- MeSH
- Anti-Bacterial Agents * pharmacology MeSH
- Bacteria drug effects MeSH
- Bacterial Infections * drug therapy microbiology therapy MeSH
- Biofilms drug effects MeSH
- Photochemotherapy * methods MeSH
- Photosensitizing Agents * pharmacology MeSH
- Humans MeSH
- Nanoparticles chemistry MeSH
- Nanostructures chemistry MeSH
- Reactive Oxygen Species metabolism MeSH
- Ultrasonic Therapy MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Many photosensitive substances suitable for photodynamic therapy (PDT) have limited applications due to their insufficient solubility in polar solvents. Our research overcomes this challenge by means of nanotechnology in order to transform hydrophobic compounds into stable aqueous solutions, enabling them to use their full potential and unique properties in cancer therapy. In this study, the novel nano-composite cGQDs-PEG-curcumin was developed to overcome the insolubility of curcumin in water and its extraordinary efficacy in PDT was evaluated. Complex characterization was performed using high-resolution transmission electron microscopy (HR-TEM), FTIR, and UV-Vis spectroscopy. Further analysis involved fluorescence lifetime imaging (FLIM), and its cellular localization was mapped with confocal microscopy. In order to evaluate PDT effectiveness, cells treated with cGQDs-PEG-curcumin were irradiated with 5 J/cm2 of 414 nm light. After irradiation, cell viability assay, scanning electron microscopy (SEM), reactive oxygen species (ROS) detection, comet assay, and γH2AX-based DNA double-strand breaks (DSBs) detection were assessed and revealed a remarkable ability of the nano-composite to induce DNA damage after irradiation without ROS production. Our findings highlight the potential of cGQDs-PEG-curcumin as a cutting-edge PDT agent, capable of disrupting cell membrane and nucleolar integrity and impairing ribosomal synthesis, which is crucial for proliferating tumour cells.
- MeSH
- Cell Nucleolus * drug effects metabolism MeSH
- DNA Breaks, Double-Stranded drug effects MeSH
- Photochemotherapy * methods MeSH
- Photosensitizing Agents * pharmacology MeSH
- Graphite * chemistry pharmacology MeSH
- Curcumin * pharmacology chemistry MeSH
- Quantum Dots * chemistry MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neoplasms * drug therapy MeSH
- Polyethylene Glycols * chemistry pharmacology MeSH
- DNA Damage * drug effects MeSH
- Reactive Oxygen Species metabolism MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
1. vydání 431 stran : ilustrace, fotografie ; 26 cm
Monografie věnovaná životu a dílu skláře, vynálezce a léčitele Antonína Rückla, propagátora helioterapie a stavitele slunečních lázní, jež došly za první republiky značné obliby, zároveň však narazily na nezájem ze strany odborné veřejnosti.
- MeSH
- Architecture history MeSH
- Heliotherapy history MeSH
- Health Resorts history MeSH
- Famous Persons MeSH
- Publication type
- Monograph MeSH
- Conspectus
- Architektura
- NML Fields
- technika
- balneologie
- dějiny lékařství
Herein, we describe and investigate biological activity of three octahedral ruthenium(II) complexes of the type [Ru(C∧N)(phen)2]+, RuL1-RuL3, containing a π-expansive cyclometalating substituted benzo[g]quinoxaline ligand (C∧N ligand) (phen = 1,10-phenanthroline). Compounds RuL1-RuL3 in cervical, melanoma, and colon human cancer cells exhibit high phototoxicity after irradiation with light (particularly blue), with the phototoxicity index reaching 100 for the complex RuL2 in most sensitive HCT116 cells. RuL2 accumulates in the cellular membranes. If irradiated, it induces lipid peroxidation, likely connected with photoinduced ROS generation. Oxidative damage to the fatty acids leads to the attenuation of the membranes, the activation of caspase 3, and the triggering of the apoptotic pathway, thus implementing membrane-localized photodynamic therapy. RuL2 is the first photoactive ruthenium-based complex capable of killing the hardly treatable colon cancer stem cells, a highly resilient subpopulation within a heterogeneous tumor mass, responsible for tumor recurrence and the metastatic progression of cancer.
- MeSH
- Apoptosis drug effects MeSH
- Cell Membrane drug effects metabolism MeSH
- Quinoxalines * chemistry pharmacology chemical synthesis MeSH
- Photochemotherapy * MeSH
- Photosensitizing Agents * pharmacology chemistry chemical synthesis therapeutic use MeSH
- Coordination Complexes * pharmacology chemistry chemical synthesis therapeutic use MeSH
- Humans MeSH
- Cell Line, Tumor MeSH
- Neoplastic Stem Cells * drug effects pathology MeSH
- Colonic Neoplasms * drug therapy pathology MeSH
- Antineoplastic Agents * pharmacology chemistry chemical synthesis therapeutic use MeSH
- Reactive Oxygen Species metabolism MeSH
- Ruthenium * chemistry pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm-2 ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment.
- MeSH
- Photochemotherapy * methods MeSH
- Photosensitizing Agents * pharmacology chemistry MeSH
- HeLa Cells MeSH
- Indoles * pharmacology chemistry MeSH
- Isoindoles * MeSH
- Humans MeSH
- Membrane Potential, Mitochondrial * drug effects MeSH
- Organometallic Compounds * pharmacology chemistry MeSH
- Oxidative Stress drug effects MeSH
- DNA Damage drug effects MeSH
- Reactive Oxygen Species * metabolism MeSH
- Zinc Compounds * pharmacology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Transcriptional profiling demonstrated markedly reduced type I IFN gene expression in untreated mycosis fungoides (MF) skin lesions compared with that in healthy skin. Type I IFN expression in MF correlated with antigen-presenting cell-associated IRF5 before psoralen plus UVA therapy and epithelial ULBP2 after therapy, suggesting an enhancement of epithelial type I IFN. Immunostains confirmed reduced baseline type I IFN production in MF and increased levels after psoralen plus UVA treatment in responding patients. Effective tumor clearance was associated with increased type I IFN expression, enhanced recruitment of CD8+ T cells into skin lesions, and expression of genes associated with antigen-specific T-cell activation. IFNk, a keratinocyte-derived inducer of type I IFNs, was increased by psoralen plus UVA therapy and expression correlated with upregulation of other type I IFNs. In vitro, deletion of keratinocyte IFNk decreased baseline and UVA-induced expression of type I IFN and IFN response genes. In summary, we find a baseline deficit in type I IFN production in MF that is restored by psoralen plus UVA therapy and correlates with enhanced antitumor responses. This may explain why MF generally develops in sun-protected skin and suggests that drugs that increase epithelial type I IFNs, including topical MEK and EGFR inhibitors, may be effective therapies for MF.
Vitiligo je častá, autoimunitně podmíněná ztráta pigmentu, která souvisí s omezením funk- ce nebo destrukcí melanocytů. V klinickém obrazu najdeme okrouhlá, oválná nebo nepravidelná bílá ložiska v úrovni okolní kůže, typicky kolem očí, na rukou, kolenou nebo genitálu. Vitiligo může doprovázet jiné autoimunitní choroby jako je Hashimotova thyreoiditida, diabetes mellitus a další
Vitiligo is a common autoimmune mediated loss of pigmentation that follows the involvement incl. destruction of melanocytes. The disease is characterized by rounded, oval or irregular white patches most frequently localized in periorbital area, hands, knees and genitals. Vitiligo could be associated with other autoimmune diseases such as Hashimoto thyroiditis, diabetes mellitus and other diseases.
Photodynamic therapy (PDT) is a clinically-approved cancer treatment that is based on production of cytotoxic reactive oxygen species to induce cell death. However, its efficiency depends on distribution of photosensitizer (PS) and depth of light penetration through the tissues. Tendency of pathological cancer tissues to exhibit lower pH than healthy tissues inspired us to explore dual-targeted pH-activatable photosensitizers based on tunable near-infrared (NIR) boron-dipyrromethene (BODIPY) dyes. Our BODIPY PSs were designed to carry three main attributes: (i) biotin or cRGD peptide as an effective cancer cell targeting unit, (ii) amino moiety that is protonated in acidic (pH <6.5) conditions for pH-activation of the PS based on photoinduced electron transfer (PET) and (iii) hydrophilic groups enhancing the water solubility of very hydrophobic BODIPY dyes. Illumination of such compounds with suitable light (>640nm) allowed for high phototoxicity against HeLa (αvβ3 integrin and biotin receptor positive) and A549 (biotin receptor positive) cells compared to healthy MRC-5 (biotin negative) cells. Moreover, no dark toxicity was observed on selected cell lines (>10 μM) providing promising photosensitizers for tumour-targeted photodynamic therapy.
- MeSH
- Biotin * chemistry MeSH
- A549 Cells MeSH
- Peptides, Cyclic chemistry pharmacology MeSH
- Photochemotherapy * MeSH
- Photosensitizing Agents * chemistry pharmacology MeSH
- HeLa Cells MeSH
- Infrared Rays MeSH
- Hydrogen-Ion Concentration MeSH
- Humans MeSH
- Boron Compounds * chemistry pharmacology MeSH
- Cell Survival drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
Plasmonic photothermal therapy (PPTT) employing plasmonic gold nanorods (GNRs) presents a potent strategy for eradication of tumors including aggressive brain gliomas. Despite its promise, there is a pressing need for a more comprehensive evaluation of PPTT using sophisticated in vitro models that closely resemble tumor tissues, thereby facilitating the elucidation of therapeutic mechanisms. In this study, we exposed 3D glioma spheroids (tumoroids) to (16-mercaptohexadecyl)trimethylammonium bromide-functionalized gold nanorods (MTAB-GNRs) and a near-infrared (NIR) laser. We demonstrate that the photothermal effect can be fine-tuned by adjusting the nanoparticle concentration and laser power. Depending on the selected parameters, the laser can trigger either regulated or non-regulated cell death (necrosis) in both mouse GL261 and human U-87 MG glioma cell lines, accompanied by translocation of phosphatidylserine in the membrane. Our investigation into the mechanism of regulated cell death induced by PPTT revealed an absence of markers associated with classical apoptosis pathways, such as cleaved caspase 3. Instead, we observed the presence of cleaved caspase 1, gasdermin D, and elevated levels of NLRP3 in NIR-irradiated tumoroids, indicating the activation of pyroptosis. This finding correlates with previous observations of lysosomal accumulation of MTAB-GNRs and the known lysosomal pathway of pyroptosis activation. We further confirmed the absence of toxic breakdown products of GNRs using electron microscopy, which showed no melting or fragmentation of gold nanoparticles under the conditions causing regulated cell death. In conclusion, PPTT using coated gold nanorods offers significant potential for glioma cell elimination occurring through the activation of pyroptosis rather than classical apoptosis pathways.
- MeSH
- Spheroids, Cellular drug effects pathology MeSH
- Photothermal Therapy MeSH
- Glioma * pathology drug therapy metabolism MeSH
- Cations chemistry pharmacology MeSH
- Metal Nanoparticles chemistry MeSH
- Quaternary Ammonium Compounds chemistry pharmacology MeSH
- Humans MeSH
- Mice MeSH
- Cell Line, Tumor MeSH
- Tumor Cells, Cultured MeSH
- Nanotubes * chemistry MeSH
- Pyroptosis * drug effects MeSH
- Cell Survival drug effects MeSH
- Gold * chemistry pharmacology MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
