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The unique characteristics of the tumor microenvironment (TME) could be exploited to develop antitumor nanomedicine strategies. However, in many cases, the actual therapeutic effect is far from reaching our expectations due to the notable tumor heterogeneity. Given the amplified characteristics of TME regulated by vascular disrupting agents (VDAs), nanomedicines may achieve unexpected improved efficacy. Herein, we fabricate platelet membrane-fusogenic liposomes (PML/DP&PPa), namely "platesomes", which actively load the hypoxia-activated pro-prodrug DMG-PR104A (DP) and physically encapsulate the photosensitizer pyropheophorbide a (PPa). Considering the different stages of tumor vascular collapse and shutdown induced by a VDA combretastatin-A4 phosphate (CA4P), PML/DP&PPa is injected 3 h after intraperitoneal administration of CA4P. First, CA4P-mediated tumor hemorrhage amplifies the enhanced permeation and retention (EPR) effect, and the platesome-biological targeting further promotes the tumor accumulation of PML/DP&PPa. Besides, CA4P-induced vascular occlusion inhibits oxygen supply, followed by photodynamic therapy-caused acute tumor hypoxia. This prolonged extreme hypoxia contributes to the complete activation of DP and then high inhibitory effect on tumor growth and metastasis. Thus, such a combining strategy of artificially-regulated TME and bio-inspired platesomes pronouncedly improves tumor drug delivery and boosts tumor hypoxia-selective activation, and provides a preferable solution to high-efficiency cancer therapy.
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RESUMEN Objetivos: Evaluar la actividad fotodinámica in vitro de la ftalocianina de aluminio tetrasulfonada clorada (AlPcClS4) sobre promastigotes y amastigotes de Leishmania (Viannia) peruviana y Leishmania (Viannia) braziliensis. Materiales y métodos: La actividad del tratamiento fotodinámico empleando AlPcClS4 sobre promastigotes y amastigotes de Leishmania fue determinada mediante el método colorimétrico Metil Tiazol Tetrazolium (MTT) y PCR cuantitativo, respectivamente. Resultados: El tratamiento fotodinámico presentó un efecto inhibitorio sobre promastigotes, principalmente sobre Leishmania (V.) peruviana, en menor proporción sobre Leishmania (V.) braziliensis y sobre las formas intracelulares de ambas especies. En Leishmania (V.) peruviana, a las 24 horas posirradiación a 200 µM y 350 µM el efecto inhibitorio fue del 72,9% y 73,9%, respectivamente y a las 96 horas fue del 78,8% y 80,6%, respectivamente. En las formas intracelulares, empleando 200 µM y evaluado a las 72 horas postratamiento, se observó una inhibición del 57,8% de amastigotes de Leishmania (V.) peruviana. El IC50 fue del 56,5; 50; 44; y 39,7 µM, que corresponde a las 24, 48, 72 y 96 horas posirradiación, respectivamente. Conclusiones: El tratamiento fotodinámico empleando AlPcClS4 frente a las especies de Leishmania presentó resultados alentadores principalmente sobre Leishmania (V.) peruviana, lo cual sugiere su potencial uso como alternativa o complemento del tratamiento convencional de la leishmaniasis tegumentaria. Sin embargo, aún se requiere continuar con nuevos ensayos para determinar el índice de selectividad sobre el parásito en su forma intracelular, y desarrollar estrategias que faciliten el ingreso eficiente de la molécula hacia la célula hospedera y al parásito.
ABSTRACT Objectives: To evaluate the in vitro photodynamic activity of aluminum phthalocyanine tetrasulfonate chloride (AlPcClS4) on promastigotes and amastigotes of Leishmania (Viannia) peruviana and Leishmania (Viannia) braziliensis. Materials and methods: The activity of photodynamic therapy using AlPcClS4 on Leishmania promastigote and amastigotes was determined by the Methyl Thiazole Tetrazolium (MTT) colorimetric method and quantitative PCR, respectively. Results: Photodynamic treatment showed an inhibitory effect on promastigotes, particularly on Leishmania (V.) peruviana, to a lesser extent on Leishmania (V.) braziliensis and also on intracellular forms of both species. At 24 hours post-radiation, using concentrations of 200 μM and 350 μM, the inhibitory effect on Leishmania (V.) peruviana was 72.9% and 73.9% respectively; at 96 hours the inhibitory effect was of 78.8% and 80.6%, respectively. Regarding intracellular forms, the inhibitory effect on Leishmania (V.) peruviana amastigotes was 57.8% at 72 hours post-treatment, using a concentration of 200 μM. The IC50 was 56.5, 50, 44 and 39.7 μM, at 24, 48, 72 and 96 hours post-radiation, respectively. Conclusions: Photodynamic therapy using AlPcClS4 against Leishmania species showed encouraging results, mainly on Leishmania (V.) peruviana, suggesting a potential use as an alternative or complement to the usual treatment of tegumentary leishmaniasis. However, new trials are still required to determine the selectivity index for the intracellular form of the parasite, and to develop methods to facilitate the efficient entry of the molecule into the host cell and the parasite.
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Leishmania braziliensis , In Vitro Techniques , Leishmaniasis , Aluminum , Photochemotherapy , Tropical Medicine , Leishmaniasis, Cutaneous , Photosensitizing AgentsABSTRACT
@#In recent years, many researchers have devoted themselves to the application of photodynamic therapy (PDT) in root canal disinfection, as conventional root canal disinfection methods have failed to achieve the optimal effect. Some clinicians have also applied PDT to root canal disinfection. PDT is expected to have a better effect than traditional root canal disinfection. This paper reviews the research progress on the mechanism, effect, influencing factors and limitations of PDT in root canal disinfection. Current research suggests that differences in the type and status of the bacteria, photosensitizers, light sources, operating environment and methods all affect the efficacy of root canal disinfection of PDT. Most of the research into PDT for root canal disinfection finds that it is effective, nontoxic, advantageous to dental pulp regeneration and comfortable for the patient, as well as lacking an excitant; however, its bactericidal effect is inferior to that of sodium hypochlorite. At present, it cannot replace traditional chemical washing but is a promising auxiliary method. The design of the photosensitizer, the energy dose of the light source and the optimal irradiation time need to be determined by further experiments, and more clinical verification is needed before its application in root canal therapy.
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Metronomic photodynamic therapy (mPDT) is a new type of photodynamic therapy (PDT) that has received much attention in recent years. It has a similar therapeutic mechanism to traditional PDT, i.e. the photosensitizer is irradiated by visible light irradiation with a specific wavelength, and tissue oxygen photochemical reactions produce cytotoxic reactive oxygen species (ROS) that selectively kill rapidly proliferating tumor cells. Unlike traditional PDT, the photosensitizer and light in mPDT are continuously transmitted at a low time and at a low rate, and the specificity of tumor treatment is enhanced by apoptosis. In this paper, the current researches on the in vitro and in vivo effects and mechanisms of mPDT, as well as the research status of photosensitizers and light sources for in vivo research, were reviewed, with a view to understanding the existing mPDT technology and providing reference for the further studies. This review paper can provide a basic for promoting the clinical research and application of mPDT.
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Photodynamic therapy (PDT), based on the photoactivation of photosensitizers (PSs), has become a well-studied therapy for cancer. Photofrin, belonging to the first generation of PS, is still widely used for the treatment of different kinds of cancers; however, it has several drawbacks that significantly limit its general clinical use. Consequently, there has been extensive research on the design of PS molecules with optimized pharmaceutical properties, with aiming of overcoming the disadvantages of traditional PS, such as poor chemical purity, long half-life, excessive accumulation into the skin, and low attenuation coefficients. The rational design of novel PS with desirable properties has attracted considerable research in the pharmaceutical field. This review presents an overview on the classical photosensitizers and the most significant recent advances in the development of PS with regard to their potential application in oncology.
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Objective To explore the therapeutic efficacy of the water soluable photosensitizer D-galactopyranosyl zinc phthalocyanines (T1)-mediated photodynamic therapy (PDT) applied to HepG2 human hepatocellular carcinoma cells in vitro and in vivo,as well as its mechanism.Methods HepG2 cells in their logarithmic growth phase were cultured and divided into different concentrations ofT1 (0 μM,0.06 μM,0.125 μM,0.25 μM,0.5 μM and 1 μM).Methyl thiazolyl tetrazolium (MTT) assays were employed to determine the effect of the T1-PDT on the proliferation of the HepG2 cells.Cell apoptosis and necrosis were measured using a cell analyzer with Annexin VFITC/PI/Hochest33342 triple-staining.The reactive oxygen species (ROS) and the mitochondrial membrane potentials of the HepG2 cells were detected using fluorescence microscopy.Confocal microscopic assays were used to observe T1's subcellular localization on the HepG2 cells.Real-time quantitative polymerase chain reactions (RT-PCRs)were used to detect any apoptosis of Bcl-2-and Bax-related genes.H-22-bearing mice were used to calculate the antitumor rate of T1-PDT,and the expression levels of Bcl-2 and Bax mRNA were detected using RT-PCRs.Twenty-four healthy mice were randomly divided into a control group,a low-dose group,a middle-dose group and a high-dose group,each of 6.Each group was given different doses of T1-PDT and the tumor inhibition rate was calculated.Results The MTT assays showed that T1-PDT could significantly inhibit HepG2 cell growth,but T1 or PDT alone had little effect.The confocal microscope assay showed that T1 was mainly localized in the mitochondria in HepG2 cells with little in the lysosome.Cell analyzer results showed that T1-PDT could induce HepG2 apoptosis.The ROS levels of HepG2 cells increased after T1-PDT.The RT-PCR results showed that T1-PDT could increase the expression of Bax and decrease the expression of Bcl-2.The in vivo experiments demonstrated that T1-PDT significantly inhibited the growth of H-22-xenografied tumors.Conclusions T1-mediated PDT has a significant lethal effect on HepG2 cells in vitro and in vitro.The lethal effect of PDT on cancer cells is shown in the apoptosis and can be attributed to T1's subcellular localization in the mitochondria,increasing ROS levels,and regulating apoptosis-related genes.
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Pigments from two different isolates of Cercospora personata CP3 & CP4 were proved to be pathogenic, toxigenic and photosensitive. Spectral characters of the pigments were studied and correlated with their phytotoxicity to groundnut leaves. The red pigment from CP4 isolates was more toxic, caused highest degree of necrosis, and was identified as cercosporin. Further cytotoxic functions of cercosporin were also studied in an attempt to understand the major cause of hepatic cancers in communities at high risk.
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BackgroundIn the present time Photodynamic therapy is a largely experimental treatment modality which is under development for application in both of neoplastic and non–neoplastic diseases. PDT involves a light-sensitive compound (photosensitizer), light and molecular oxygen. The photosensitizer is excited to its singlet state by light of the appropriate wavelength. Responses to photodynamic treatment are dependent on the photosensitizer used the an illumination conditions, the oxygenation status of the tissue and the type of cells involved.CoalTo study new photosensitizers from the pyrazole derivatives which is based on chlorine and porphyrin and produced from sea algae to the lung cancer cell (A549) that is cultured in vitro medium and tested by two ways that are light treatment and dark treatment. Furthermore we define how the photosensitizer dictate cancer cells by test MTT/3-/4.5-dimethylthiazole-2- yl/-2.5-biphenyl tetrzolium bromide a yellow tetrazole/, and how to change the cell morphological characteristics by its micro photo and determine potosensitizers that dictates on the least doze of the cell.Materials and MethodsThe cell line tested was A549 (human lung carcinoma cell). The cell line was obtained from the cell line bank at Seoul National University’s Cancer Research Center (Korea) and were grown in medium RPMI-1640 (Sigma-Aldrich) with 10% fetal bovine serum, glutamine, penicillin and streptomycin at 37 0C in humidified atmosphere of 5% CO2 in air. Phosphate buffered saline (PBS) (Sigma-Aldrich), microscope (Olympus, CK40-32 PH, Japan), Laser irradiation (BioSpec LED 670-700 nm, Russia), ELISA-reader (BioTek, Synergy HT, USA), trypsin-EDTA solution, incubator (37 0C, 5% CO2) were used. The PDT was carried out using a diode laser generator apparatus (BioSpec LED, Russia) equipped with a halogen lamp, a band-pass filter (670-700 nm), and a fiber optics bundle. The wavelength was set at 670±1 nm. Duration of the light irradiation, under PDT treatment, is calculated taking into account the empirically found effective dose of light energy in J/cm2. Figure 1 shows micrographs from an optical microscope illustrating the morphological changes of A549 cells at different points of time after PDT.ResultsThe morphological changes for all tested photosensitizers were revealed by the same patterns, hence we have shown the morphological changes for compound 8 in this paper (Fig 1). Untreated A549 cells as a control did not show any significant morphological changes. The changes in the state and activity of cellular organelles induced by PDT were clearly observed after 3 h. PDT treatment against A549 cells induced plasma membrane disruption and cell shrinkage, indicating the plasma membrane as the main target for the photosensitizer: the membrane of A549 cells began to shrink immediately after PDT, and cell death processes commenced with cytoplasm leakage around the membrane for the first 3 h. After 24 h, the membrane had disintegrated, confirming the loss of cell viability.СоnclusionThe morphological changes were determined in 3 h, 24 h and 48 h after PDT. The bioactivity of 23 new photosensitizers was examined. Among them, 8 photosensitizers showed a promising effect for PDT, therefore, their in vitro biological results are displayed in this study. It was observed from the experimental results that the tested photosensitizers showed more promising effects for PDT or light toxicity. These photosensitizers inhibited more than 50% cells at 2.5 μM after 24 h. Untreated cells as control did not show any significant morphological changes. The PDT treatment cells induced to plasma membrane disruption and cell shrinkage. After 24 h of treatment the membrane was disintegrated, and confirmed the loss of cell viability.
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Mechanical removal of the biofilm and adjunctive use of antibacterial disinfectants or various antibiotics have been conventional methods of the periodontitis therapy. There has been an upsurge of bacterial strains becoming resistant due to the injudicious use of antibiotics, recently. As a result there is pronounced interest and keenness in the development of alternate antimicrobial concepts. As the scientific community seeks alternatives to antibiotic treatment, periodontal researchers have found that photodynamic therapy (PDT) is advantageous to suppress anaerobic bacteria. Hence, PDT could be an alternative to conventional periodontal therapeutic methods. This review elucidates the evolution and use of photo dynamic therapy. The application of photosensitizing dyes and their excitation by visible light enables effective killing of periodontopathogens. Even though PDT is still in the experimental stages of development and testing, the method may be an adjunct to conventional antibacterial measures in periodontology. PDT application has an adjunctive benefit besides mechanical treatment at sites with difficult access. Necessity for flap operations may be reduced, patient comfort may increase and treatment time decrease. Clinical follow-up studies are needed to confirm the efficacy of the procedure.
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Bacteria, Anaerobic/drug effects , Biofilms/drug effects , Drug Resistance, Microbial , Furcation Defects/drug therapy , Humans , Periodontitis/drug therapy , Photochemotherapy , Photosensitizing Agents/pharmacology , Photosensitizing Agents/therapeutic useABSTRACT
BACKGROUND AND OBJECTIVES: The 9-Hydroxypheophorbide-alpha(9-HpbD-alpha) is a new photosensitizer, derived from a plant in water. We conducted a series of experiments in vivo to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-alpha and 630 nm diode laser on squamous cell carcinoma. MATERIALS AND METHOD: SNU-1041 cell line was heterotransplanted into the subcutaneous space of nude mouse. When the tumors grew up to 400 mm3, the animals were randomly seperated into 4 groups: Group I (n=5) of the normal control group;Group II (n=10), which received interstitial injection of 0.007 microgram/mm3 of 9-HpbD-alpha;Group III (n=10), which received irradiation with 1.6 J/mm3 of light using diode laser;Group IV (n=10), which received interstitial injection of 0.007 microgram/mm3 of 9-HpbD-alpha followed by irradiation with 1.6 J/mm3 of light 6 hours after the injection. After photodynamic therapy (PDT), tumor tissue was harvested for histopathologic study under light microscopy and transmission electron microscope (TEM). RESULTS: PDT group (Group IV) showed significant remission rate (70 %), compared to control group (p<0.05). The microscopic findings of the tumor section were characterized by massive necrosis and some apoptotic cells among the normal cells. TEM showed different morphologic changes between necrotic and apoptotic cells. These findings were considered as the evidence of direct cytotoxicity of PDT using 9-HpbD-alpha and 630 nm diode laser. CONCLUSION: The results suggest that therapy using PDT, 9-HpbD-alpha and diode laser shows an anticancer effect. Its therapeutic mechanism appears to be based on necrosis that is caused by direct cytotoxicity.
Subject(s)
Animals , Mice , Carcinoma, Squamous Cell , Cell Line , Head , Lasers, Semiconductor , Mice, Nude , Microscopy , Neck , Necrosis , Photochemotherapy , Photosensitizing Agents , PlantsABSTRACT
Photodynamic therapy (PDT) was first used for the treatment of esophageal cancer in early 1980s, Since then, numerous applications have been reported for its use in gastrointestinal tract including Barrett's esophagus, gastric, duodenal, biliary, pancreatic and colorectal lesions. PDT in gastroenterology has made tremendous progress over the last decade but its clear role is yet to be proved. Now, there is an increasing need for less invasive methods of treatment in patients with pre-malignant disease, early cancer or those who are unfit for surgery. It is one of a number of ablative techniques currently under investigation and appears to have a number of potential advantages over other forms of treatment in the alimentary tract. The development of newer potent, highly efficient photosensitizers, as well as endoscopic imaging techniques and light delivery systems, are continuing to expand the clinical uses of PDT. As data from additional clinical trials become available, we will gain a clearer perspective of where PDT fits in the treatment of cancers.