A second-generation series of biscyclometalated 2-(5-aryl-thienyl)-benzimidazole and -benzothiazole Ir(III) dppz complexes [Ir(C^N)2(dppz)]+, Ir1-Ir4, were rationally designed and synthesized, where the aryl group attached to the thienyl ring was p-CF3C6H4 or p-Me2NC6H4. These new Ir(III) complexes were assessed as photosensitizers to explore the structure-activity correlations for their potential use in biocompatible anticancer photodynamic therapy. When irradiated with blue light, the complexes exhibited high selective potency across several cancer cell lines predisposed to photodynamic therapy; the benzothiazole derivatives (Ir1 and Ir2) were the best performers, Ir2 being also activatable with green or red light. Notably, when irradiated, the complexes induced leakage of lysosomal content into the cytoplasm of HeLa cancer cells and induced oncosis-like cell death. The capability of the new Ir complexes to photoinduce cell death in 3D HeLa spheroids has also been demonstrated. The investigated Ir complexes can also catalytically photo-oxidate NADH and photogenerate 1O2 and/or •OH in cell-free media.
- MeSH
- antitumorózní látky farmakologie MeSH
- benzothiazoly MeSH
- fotosenzibilizující látky farmakologie terapeutické užití MeSH
- fototoxická dermatitida farmakoterapie MeSH
- iridium farmakologie MeSH
- komplexní sloučeniny farmakologie MeSH
- lidé MeSH
- lyzozomy MeSH
- nádorové buněčné linie MeSH
- nádory farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Photodynamic therapy is an alternative treatment mainly for cancer but also for bacterial infections. This treatment dates back to 1900 when a German medical school graduate Oscar Raab found a photodynamic effect while doing research for his doctoral dissertation with Professor Hermann von Tappeiner. Unexpectedly, Raab revealed that the toxicity of acridine on paramecium depends on the intensity of light in his laboratory. Photodynamic therapy is therefore based on the administration of a photosensitizer with subsequent light irradiation within the absorption maxima of this substance followed by reactive oxygen species formation and finally cell death. Although this treatment is not a novelty, there is an endeavor for various modifications to the therapy. For example, selectivity and efficiency of the photosensitizer, as well as irradiation with various types of light sources are still being modified to improve final results of the photodynamic therapy. The main aim of this review is to summarize anticancer and antibacterial modifications, namely various compounds, approaches, and techniques, to enhance the effectiveness of photodynamic therapy.
- MeSH
- antibakteriální látky farmakologie terapeutické užití MeSH
- buněčná smrt MeSH
- fotochemoterapie metody MeSH
- fotosenzibilizující látky farmakologie terapeutické užití MeSH
- lidé MeSH
- nádory farmakoterapie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
The strong antifungal effect of sulfonated polystyrene nanoparticles (NPs) with an encapsulated tetraphenylporphyrin (TPP) photosensitizer is reported here. TPP is activated by visible light, resulting in the generation of singlet oxygen. Its antifungal action is potentiated in the presence of potassium iodide, yielding I2/I3−, another antifungal species. The NPs exhibit no dark toxicity, but a broad spectrum of antifungal photodynamic effects. The efficiency of this rapid killing (on the order of minutes) depends on the concentration of TPP NPs, potassium iodide, yeast species and temperature. A strong antifungal activity of TPP NPs is demonstrated on eleven pathogenic and opportunistic pathogenic yeast species (six Candida species and other yeast species, including melanized Hortaea werneckii). The composition and architecture of yeast cell envelope structures clearly influence the efficacy of photodynamic therapy. Candida krusei is the most sensitive to photodynamic therapy. Despite expectations, melanin does not provide Hortaea cells with marked resistance compared to white yeast species. The kinetics of the interaction of NPs with yeast cells is also described. This study may inspire and promote the fabrication of a new type of antiseptic for various skin injuries in clinical medicine.
PURPOSE OF REVIEW: Transurethral resection of bladder cancer (TURBT) is in its standard form an inherently imperfect technique. Fluorescence-guided photodynamic diagnosis (PDD) represents one way to improve the outcome by enhancing tumour detection. Fluorescence has been used in connection with bladder cancer since the 1970s, with a number of studies being published since then. However, the method is still not recommended as a standard part of TURBT mainly because of the limited level of evidence of concerned studies, questionable cost-effectiveness and even contradictory results. The review lists the latest articles covering this topic. RECENT FINDINGS: Several recently published meta-analyses reviewed a series of randomized controlled trials (RCTs) concerning PDD assisted TURBT. Results were generally supporting the positive effect on reduction of recurrence rate. However, the mentioned meta-analyses are overlapping in terms of reviewed RCT that provide only a low level of evidence according to a recent Cochrane review. Supposed limitations of PDD (timing of the procedure, low specificity) and possible solutions are also covered. SUMMARY: Most of the published data confirmed reduced early recurrence rate after PDD assisted TURBT comparing to standard TURBT. Its impact on late recurrence rate, progression rate or cost-effectiveness has not been sufficiently demonstrated.
- MeSH
- cystektomie metody MeSH
- fluorescence MeSH
- fotosenzibilizující látky MeSH
- lidé MeSH
- lokální recidiva nádoru epidemiologie prevence a kontrola patologie MeSH
- nádory močového měchýře patologie MeSH
- transuretrální resekce močového měchýře MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
A small series of N-aryl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-amines was synthesized from easily accessible 1-phenyl-1H-pyrazol-3-ol via 7-iodo-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine and 7-iodo-4-methyl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridine intermediates and their subsequent use in palladium catalyzed Buchwald-Hartwig cross-coupling reaction with various anilines. Majority of the compounds were not significantly cytotoxic to melanoma G361 cells in the dark up to 10 μM concentration, but their activity could be increased by irradiation with visible blue light (414 nm). The most active compound 10 possessed EC50 values of 3.5, 1.6 and 0.9 μM in cells irradiated with 1, 5 and 10 J/cm2, respectively. The treatment caused generation of reactive oxygen species in cells and extensive DNA damage, documented by the comet assay and by detection of phosphorylated histone H2A.X, followed by apoptotic cell death. Our results suggest that N-aryl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-amines could serve as a potential source of photosensitizing compounds with anticancer activities.
- MeSH
- antitumorózní látky chemická syntéza chemie farmakologie MeSH
- fotochemoterapie MeSH
- fotosenzibilizující látky chemická syntéza chemie farmakologie MeSH
- léky antitumorózní - screeningové testy MeSH
- lidé MeSH
- melanom farmakoterapie metabolismus patologie MeSH
- molekulární struktura MeSH
- nádorové buňky kultivované MeSH
- nádory kůže farmakoterapie metabolismus patologie MeSH
- proliferace buněk účinky léků MeSH
- světlo MeSH
- viabilita buněk účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- vztahy mezi strukturou a aktivitou MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Two alkylated verdazyl radicals (AlkVZs) were investigated as active compounds for photoinitiated controlled MCF-7 cell death. Observed results unambiguously showed that AlkVZ could be a potential structural moiety for the design of a novel family of photodynamic therapy agents. The main advantage of the proposed substances is an oxygen-independent generation of active radicals, which play a pivotal role in the treatment of oxygen-deficient tumors.
Radiation (RT) remains the most frequently used treatment against cancer. The main limitation of RT is its lack of specificity for cancer tissues and the limited maximum radiation dose that can be safely delivered without damaging the surrounding healthy tissues. A step forward in the development of better RT is achieved by coupling it with other treatments, such as photodynamic therapy (PDT). PDT is an anti-cancer therapy that relies on the light activation of non-toxic molecules-called photosensitizers-to generate ROS such as singlet oxygen. By conjugating photosensitizers to dense nanoscintillators in hybrid architectures, the PDT could be activated during RT, leading to cell death through an additional pathway with respect to the one activated by RT alone. Therefore, combining RT and PDT can lead to a synergistic enhancement of the overall efficacy of RT. However, the involvement of hybrids in combination with ionizing radiation is not trivial: the comprehension of the relationship among RT, scintillation emission of the nanoscintillator, and therapeutic effects of the locally excited photosensitizers is desirable to optimize the design of the hybrid nanoparticles for improved effects in radio-oncology. Here, we discuss the working principles of the PDT-activated RT methods, pointing out the guidelines for the development of effective coadjutants to be tested in clinics.
Ciele: Vyhodnotenie viditeľnosti a hĺbky demarkačnej línie v stróme rohovky u očí s keratokónusom 1 mesiac a 3 mesiace po akcelerovanom rohovkovom cross-linkingu (ACXL) s abráziou s použitím prednosegmentovej optickej koherentnej tomografie (AS OCT). Materiál a metódy: Práca analyzuje skupinu 34 očí s keratokónusom 1 mesiac a 3 mesiace po ACXL (9mW/cm2počas 10min). Skupinu bola klasifikovaná na základe ABCD klinickej klasifikácie keratokónusu podľa Belina a Duncana. AS OCT (Zeiss Cirrus 500, Anterior Segment Premier module) bola použitá na posúdenie viditeľnosti a presnej hĺbky demarkačnej línie v stróme rohovky. Výsledky: Demarkačná línia bola 1 mesiac po ACXL viditeľná u 76,5 % očí s priemernou hĺbkou 238.13 ±20.36 μm a 3 mesiace po ACXL u 100 % očí s priemernou hĺbkou 263,43 ±12,59 μm. Štatistická analýza skupiny nepreukázala signifikantný vzťah medzi štádiom ochorenia a viditeľnosťou demarkačnej línie, avšak v súbore bola tendencia k vyššiemu veku (> 30 rokov) u tých očí, kde bola demarkačná línia viditeľná v porovnaní s očami, kde bola demarkačná línia len čiastočne viditeľná 3 mesiace po ACXL. Nezistili sme rozdiel v priemernej, ani v maximálnej hĺbke línie pri porovnaní 1 mesiac a 3 mesiace po zákroku. V súbore nebol zaznamenaný žiadny prípad progresie ochorenia 3 mesiace po ACXL. Záver: Naša štúdia naznačuje, že hodnotenie demarkačnej línie v stróme rohovky je spoľahlivejšie 3 mesiace po ACXL v porovnaní s hodnotením 1 mesiac po zákroku. Zároveň sme zaznamenali tendenciu k vyššiemu veku pacientov v prípade očí, kde bola demarkačná línia zreteľne viditeľná 3 mesiace po ACXL. Nepotvrdili sme vzťah medzi štádiom keratokónusu a hĺbkou línie, ani rozdiel v jej priemernej a maximálnej hĺbke 1 mesiac a 3 mesiace po zákroku.
Objectives: Evaluation of the visibility and depth of the demarcation line in the corneal stroma in eyes with keratoconus 1 month and 3 months after epi-off accelerated corneal cross-linking (ACXL) using anterior segment optical coherence tomography (AS OCT). Material and Methods: This study analyses a group of 34 eyes with keratoconus 1 month and 3 months after ACXL (9 mW/cm2 for 10 min). The group was classified based on the ABCD clinical classification of keratoconus according to Belin and Duncan. AS OCT (ZeissCirrus 500, Anterior Segment Premier module) was used to assess the visibility and exact depth of the demarcation line in the corneal stroma. Results: The demarcation line was visible 1 month after ACXL in 76.5% of eyes with a mean depth of 238.13 ±20.36 μm and 3 months after ACXL in 100% of eyes with a mean depth of 263.43 ±12.59 μm. Statistical analysis of the group did not show a significant relationship between the disease stage and the demarcation line visibility; however, there was a trend towards higher age (>30 years) in the group in those eyes where the demarcation line was visible vs. partially visible 3 months after ACXL. We found no difference in the mean and maximum line depth when comparing 1 month and 3 months after the procedure. There were no cases of disease progression 3 months after ACXL in the group. Conclusion: Our study suggests that the assessment of the demarcation line in the corneal stroma is more reliable 3 months compared to 1 month after ACXL. We also observed a trend towards higher patient age in eyes where the demarcation line was clearly visible 3 months after ACXL. We did not confirm a relationship between the stage of keratoconus and the depth of the line, nor a difference in its mean and maximum depth 1 month and 3 months after the procedure.
Combating biofilm infections remains a challenge due to the shield and acidic conditions. Herein, an acid-responsive nanoporphyrin (PN3-NP) based on the self-assembly of a water-soluble porphyrin derivative (PN3) is constructed. Additional kinetic control sites formed by the conjugation of the spermine molecules to a porphyrin macrocycle make PN3 self-assemble into stable nanoparticles (PN3-NP) in the physiological environment. Noteworthily, near-infrared (NIR) fluorescence monitoring and synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) effects of PN3-NP can be triggered by the acidity in biofilms, accompanied by intelligent transformation into dot-like nanospheres. Thus, damage to normal tissue is effectively avoided and accurate diagnosis and treatment of biofilms is achieved successfully. The good results of fluorescence imaging-guided photo-ablation of antibiotic-resistant strains methicillin-resistant Staphylococcus aureus (MRSA) biofilms verify that PN3-NP is a promising alternative to antibiotics. Meanwhile, this strategy also opens new horizons to engineer smart nano-photosensitizer for accurate diagnosis and treatment of biofilms.
- MeSH
- antibakteriální látky farmakologie MeSH
- biofilmy MeSH
- fotochemoterapie metody MeSH
- fotosenzibilizující látky farmakologie MeSH
- fototerapie metody MeSH
- methicilin rezistentní Staphylococcus aureus MeSH
- porfyriny farmakologie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
PURPOSE: In ophthalmology, data from both eyes of a person are frequently included in the statistical evaluation. This violates the requirement of data independence for classical statistical tests (e.g. t-Test or analysis of variance (ANOVA)) because it is correlated data. Linear mixed models (LMM) were used as a possibility to include the data of both eyes in the statistical evaluation. METHODS: The LMM is available for a variety of statistical software such as SPSS or R. The application was applied to a retrospective longitudinal analysis of an accelerated corneal cross-linking (ACXL (9*10)) treatment in progressive keratoconus (KC) with a follow-up period of 36 months. Forty eyes of 20 patients were included, whereas sequential bilateral CXL treatment was performed within 12 months. LMM and ANOVA for repeated measurements were used for statistical evaluation of topographical and tomographical data measured by Pentacam (Oculus, Wetzlar, Germany). RESULTS: Both eyes were classified into a worse and better eye concerning corneal topography. Visual acuity, keratometric values and minimal corneal thickness were statistically significant between them at baseline (p < 0.05). A significant correlation between worse and better eye was shown (p < 0.05). Therefore, analyzing the data at each follow-up visit using ANOVA partially led to an overestimation of the statistical effect that could be avoided by using LMM. After 36 months, ACXL has significantly improved BCVA and flattened the cornea. CONCLUSION: The evaluation of data of both eyes without considering their correlation using classical statistical tests leads to an overestimation of the statistical effect, which can be avoided by using the LMM.
- MeSH
- fotochemoterapie MeSH
- fotosenzibilizující látky terapeutické užití MeSH
- keratokonus diagnóza farmakoterapie MeSH
- kolagen terapeutické užití MeSH
- lidé MeSH
- reagencia zkříženě vázaná terapeutické užití MeSH
- retrospektivní studie MeSH
- riboflavin terapeutické užití MeSH
- rohovka MeSH
- rohovková topografie MeSH
- ultrafialové záření MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
