Graphene-Based Photodynamic Therapy and Overcoming Cancer Resistance Mechanisms: A Comprehensive Review.

Photodynamic therapy (PDT) is a non-invasive therapy that has made significant progress in treating different diseases, including cancer, by utilizing new nanotechnology products such as graphene and its derivatives. Graphene-based materials have large surface area and photothermal effects thereby making them suitable candidates for PDT or photo-active drug carriers. The remarkable photophysical properties of graphene derivates facilitate the efficient generation of reactive oxygen species (ROS) upon light irradiation, which destroys cancer cells. Surface functionalization of graphene and its materials can also enhance their biocompatibility and anticancer activity. The paper delves into the distinct roles played by graphene-based materials in PDT such as photosensitizers (PS) and drug carriers while at the same time considers how these materials could be used to circumvent cancer resistance. This will provide readers with an extensive discussion of various pathways contributing to PDT inefficiency. Consequently, this comprehensive review underscores the vital roles that graphene and its derivatives may play in emerging PDT strategies for cancer treatment and other medical purposes. With a better comprehension of the current state of research and the existing challenges, the integration of graphene-based materials in PDT holds great promise for developing targeted, effective, and personalized cancer treatments.

Hyperoside as a UV Photoprotective or Photostimulating Compound-Evaluation of the Effect of UV Radiation with Selected UV-Absorbing Organic Compounds on Skin Cells.

Ultraviolet (UV) radiation is a non-ionizing radiation, which has a cytotoxic potential, and it is therefore necessary to protect against it. Human skin is exposed to the longer-wavelength components of UV radiation (UVA and UVB) from the sun. In the present paper, we focused on the study of eight organic UV-absorbing compounds: astragalin, beta-carotene, 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, hyperoside, 3-(4-methylbenzylidene)camphor, pachypodol, and trans-urocanic acid, as possible protectives of skin cells against UVA and UVB radiation. Their protective effects on skin cell viability, ROS production, mitochondrial membrane potential, liposomal permeability, and DNA integrity were investigated. Only some of the compounds studied, such as trans-urocanic acid and hyperoside, had a significant effect on the examined hallmarks of UV-induced cell damage. This was also confirmed by an atomic force microscopy study of morphological changes in HaCaT cells or a study conducted on a 3D skin model. In conclusion, hyperoside was found to be a very effective UV-protective compound, especially against UVA radiation. Commonly used sunscreen compounds such as 2,4-dihydroxybenzophenone, 2-hydroxy-4-methoxybenzophenone, and 3-(4-methylbenzylidene)camphor turned out to be only physical UV filters, and pachypodol with a relatively high absorption in the UVA region was shown to be more phototoxic than photoprotective.

Photodynamic therapy: Innovative approaches for antibacterial and anticancer treatments.

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.

Acute pre-exercise hydrogen rich water intake does not improve running performance at maximal aerobic speed in trained track and field runners: A randomized, double-blind, placebo-controlled crossover study.

PURPOSE: This study investigated the effects of acute, pre-exercise, hydrogen rich water (HRW) ingestion on running time to exhaustion at maximal aerobic speed in trained track and field runners. METHODS: Twenty-four, male runners aged 17.5 ± 1.8 years, with body mass index = 21.0 ± 1.3 kg⋅m-2, and maximal oxygen uptake = 55.0 ± 4.6 ml⋅kg-1⋅min-1 (mean ± standard deviation) participated in this randomized, double-blind, placebo-controlled crossover study. All runners ingested 1260 ml of HRW which was divided into four doses and taken at 120 min (420 ml), 60 min (420 ml), 30 min (210 ml), and 10 min (210 ml) prior to exercise. The running protocol consisted of three phases: warm-up performed at 10 km⋅h-1 for 3 min, followed by a transition phase performed at an individually determined speed (10 km⋅h-1 + maximal aerobic speed)/2 for 1 min, and finally the third phase performed at individual maximal aerobic speed until exhaustion. Time to exhaustion, cardiorespiratory variables, and post-exercise blood lactate concentration were measured. RESULTS: When running to exhaustion at maximal aerobic speed, compared with placebo, HRW had no significant effects on the following variables: time to exhaustion (217 ± 49 and 227 ± 53 s, p = 0.20), post-exercise blood lactate concentration (9.9 ± 2.2 and 10.1 ± 2.0 mmol⋅L-1, p = 0.42), maximal heart rate (186 ± 9 and 186 ± 9 beats⋅min-1, p = 0.80), and oxygen uptake (53.1 ± 4.5 and 52.2 ± 4.7 ml⋅kg-1⋅min-1, p = 0.33). No variable assessed as a candidate moderator was significantly correlated with time to exhaustion (Spearman's correlation coefficients ranged from -0.28 to 0.30, all p ≥ 0.16). CONCLUSIONS: Pre-exercise administration of 1260 ml of HRW showed no ergogenic effect on running performance to exhaustion at maximal aerobic speed in trained track and field runners.

Biological Evaluation of Photodynamic Effect Mediated by Nanoparticles with Embedded Porphyrin Photosensitizer.

Clinically approved photodynamic therapy (PDT) is a minimally invasive treatment procedure that uses three key components: photosensitization, a light source, and tissue oxygen. However, the photodynamic effect is limited by both the photophysical properties of photosensitizers as well as their low selectivity, leading to damage to adjacent normal tissue and/or inadequate biodistribution. Nanoparticles (NPs) represent a new option for PDT that can overcome most of the limitations of conventional photosensitizers and can also promote photosensitizer accumulation in target cells through enhanced permeation and retention effects. In this in vitro study, the photodynamic effect of TPP photosensitizers embedded in polystyrene nanoparticles was observed on the non-tumor NIH3T3 cell line and HeLa and G361 tumor cell lines. The efficacy was evaluated by viability assay, while reactive oxygen species production, changes in membrane mitochondrial potential, and morphological changes before and after treatment were imaged by atomic force microscopy. The tested nanoparticles with embedded TPP were found to become cytotoxic only after activation by blue light (414 nm) due to the production of reactive oxygen species. The photodynamic effect observed in this evaluation was significantly higher in both tumor lines than the effect observed in the non-tumor line, and the resulting phototoxicity depended on the concentration of photosensitizer and irradiation time.

Synthesis of N-aryl-2,6-diphenyl-2H-pyrazolo[4,3-c]pyridin-7-amines and their photodynamic properties in the human skin melanoma cell line G361.

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.

Differences in the Effects of Broad-Band UVA and Narrow-Band UVB on Epidermal Keratinocytes.

BACKGROUND: The sun is a natural source of UV radiation. It can be divided into three bands, UVA (315-400 nm), UVB (280-315 nm) and UVC (100-280 nm), where the radiation up to 290 nm is very effectively eliminated by the stratospheric ozone. Although UV radiation can have a beneficial effect on our organism and can be used in the treatment of several skin diseases, it must primarily be considered harmful. METHODS: In the presented work, we focused on the study of the longer-wavelength UV components (UVA and UVB) on the human epidermal keratinocyte line HaCaT. As UVA and UVB radiation sources, we used commercially available UVA and UVB tubes from Philips (Philips, Amsterdam, The Netherlands), which are commonly employed in photochemotherapy. We compared their effects on cell viability and proliferation, changes in ROS production, mitochondrial function and the degree of DNA damage. RESULTS: Our results revealed that UVB irradiation, even with significantly lower irradiance, caused greater ROS production, depolarization of mitochondrial membrane potential and greater DNA fragmentation, along with significantly lowering cell viability and proliferative capacity. CONCLUSIONS: These results confirm that UV radiation causes severe damages in skin cells, and they need to be protected from it, or it needs to be applied more cautiously, especially if the component used is UVB.

The effect of two porphyrine photosensitizers TMPyP and ZnTPPS4 for application in photodynamic therapy of cancer cells in vitro.

Photodynamic therapy (PDT) is one of the treatments for cancer. This therapy uses a combination of a photosensitizer (PS), light irradiation, and oxygen O2, which is converted to cytotoxic 1O2 and other forms of reactive oxygen species (ROS), causing selective damage to the target tissue. In this work, we studied effect of two porphyrin photosensitizers TMPyP and ZnTPPS4 at three different concentrations (0.25, 0.5, 5µM) after two irradiation doses (5 and 25 J/cm2). Photodynamic efect of TMPyP and ZnTPPS4 were confirmed by a battery of in vitro tests including MTT, reactive oxygen species (ROS) production and mitochondrial membrane potential test (MMP). Morphological changes of the cells before and after treatment were imaged by atomic force microscopy (AFM). The most effective combination of irradiation dose and concentration for both PSs showed a concentration of 5 µM and a irradiation dose of 25 J/cm2 in both cell cultures.

Effects of zinc porphyrin and zinc phthalocyanine derivatives in photodynamic anticancer therapy under different partial pressures of oxygen in vitro.

Photodynamic therapy (PDT) is gradually becoming an alternative method in the treatment of several diseases. Here, we investigated the role of oxygen in photodynamically treated cervical cancer cells (HeLa). The effect of PDT on HeLa cells was assessed by exposing cultured cells to disulphonated zinc phthalocyanine (ZnPcS2) and tetrasulphonated zinc tetraphenylporphyrin (ZnTPPS4). Fluorescence microscopy revealed their different localizations within the cells. ZnTPPS4 seems to be mostly limited to the cytosol and lysosomes, whereas ZnPcS2 is most likely predominantly attached to membrane structures, including plasmalemma and the mitochondrial membrane. Phototoxicity assays of PDT-treated cells carried out under different partial pressures of oxygen showed dose-dependent responses. Interestingly, ZnPcS2 was also photodynamically effective at a minimal level of oxygen, under a nitrogen atmosphere. On the other hand, hyperbaric oxygenation did not lead to a higher PDT efficiency of either photosensitizer. Although both photosensitizers can induce a significant drop in mitochondrial membrane potential, ZnPcS2 has a markedly higher effect on mitochondrial respiration that was completely blocked after two short light cycles. In conclusion, our observations suggest that PDT can be effective even in hypoxic conditions if a suitable sensitizer is chosen, such as ZnPcS2, which can inhibit mitochondrial respiration.

The application of antimicrobial photodynamic inactivation on methicillin-resistant S. aureus and ESBL-producing K. pneumoniae using porphyrin photosensitizer in combination with silver nanoparticles.

As resistance of bacterial strains to antibiotics is a major problem, there is a need to look for alternative treatments. One option is antimicrobial photodynamic inactivation (aPDI). The pathogenic cells are targeted by a nontoxic photosensitizer while the surrounding healthy tissue is relatively unaffected. The photosensitizer is activated by light of t appropriate wavelength resulting in the generation of reactive oxygen species that are cytotoxic for the pathogens. In this work, the photosensitizer TMPyP and silver nanoparticles (AgNPs) were investigated for their synergistic antibacterial effect. We tested these two substances on two bacterial strains, methicillin-resistant Staphylococcus aureus 4591 (MRSA) and extended-spectrum beta-lactamases-producing Klebsiella pneumoniae 2486 (ESBL-KP), to compare their effectiveness. The bacteria were first incubated with TMPyP for 45 min or 5 h, then irradiated with a LED source with the total fluence of 10 or 20 J/cm2 and then placed in a microbiological growth medium supplemented with AgNPs. To accomplish the synergistic effect, the optimal combination of TMPyP and AgNPs was estimated as 1.56-25 µM for TMPyP and 3.38 mg/l for AgNPs in case of MRSA and 1.56-50 µM for TMPyP and 3.38 mg/l for AgNPs in case of ESBL-KP at 45 min incubation with TMPyP and fluence of 10 J/cm2. Longer incubation and/or longer irradiation led to a decrease in the maximum values of the photosensitizer concentration to produce the synergistic effect. From this work it can be concluded that the combination of antimicrobial photodynamic inactivation with a treatment including silver nanoparticles could be a promising approach to treat bacterial infection.

Adverse Phototoxic Effect of Essential Plant Oils on NIH 3T3 Cell Line after UV Light Exposure.

AIM: Natural or artificial substances have become an inseparable part of our lives. It is questionable whether adequate testing has been performed in order to ensure these substances do not pose a serious health risk. The principal aim of our research was to clarify the potential risk of adding essential oils to food, beverages and cosmetic products. METHODS: The toxicity of substances frequently employed in cosmetics, aromatherapy and food industry (bergamot oil, Litsea cubeba oil, orange oil, citral) were investigated using cell line NIH3T3 (mouse fibroblasts) with/without UV irradiation. The MTT assay was used to estimate the cell viability. Reactive oxygen species (ROS) which are products of a number of natural cellular processes such as oxygen metabolism and inflammation were measured to determine the extent of cellular stress. DNA damage caused by strand breaks was examined by comet assay. RESULTS: MTT test determined EC50 values for all tested substances, varying from 0.0023% v/v for bergamot oil to 0.018% v/v for citral. ROS production measurement showed that UV radiation induces oxidative stress to the cell resulting in higher ROS production compared to the control and non-irradiated samples. Comet assay revealed that both groups (UV, without UV) exert irreversible DNA damage resulting in a cell death. CONCLUSIONS: Our findings suggest that even low concentrations (lower than 0.0464% v/v) of orange oil can be considered as phototoxic (PIF value 8.2) and probably phototoxic for bergamot oil (PIF value 4.6). We also found significant changes in the cell viability, the ROS production and the DNA after the cells were exposed to the tested chemicals. Even though these substances are widely used as antioxidants it should be noted that they present a risk factor and their use in cosmetic and food products should be minimized.

C-MYC and C-FOS expression changes and cellular aspects of the photodynamic reaction with photosensitizers TMPyP and ClAlPcS2.

Photodynamic therapy (PDT) is based on the tumor-selective accumulation of photosensitizer followed by irradiation with light of an appropriate wavelength. After irradiation and in the presence of oxygen, photosensitizer induces cellular damage. The aim of this study was to evaluate effects of two photosensitizers TMPyP and ClAlPcS2 on cell lines to obtain better insight into their mechanisms of action. We determined cell viability, reactive oxygen species (ROS) generation and changes in expression levels of two important early response genes, C-MYC and C-FOS, on tumor MCF7 (human breast adenocarcinoma) and G361 (human melanoma) cell lines and non-tumor BJ cell line (human fibroblast) after photodynamic reaction with TMPyP and ClAlPcS2 as photosensitizers. In addition TMPyP and ClAlPcS2 cellular uptake and clearance and antioxidant capacity of the mentioned cell lines were investigated. We found appropriate therapeutic doses and confirmed that both tested photosensitizers are photodynamically efficient in treatment used cells in vitro. TMPyP is more efficient; it had higher ROS production and toxicity after irradiation by intermediate therapeutic doses than ClAlPcS2. We revealed that both TMPyP and ClAlPcS2-PDT increased C-FOS expression on tumor cell lines (G361 and MCF7), but not on non-tumor BJ cell line. Conversely, both TMPyP and ClAlPcS2-PDT decreased C-MYC expression on non-tumor BJ cell line but not on tumor cell lines. As first we tested these photosensitizers in such extent and we believe that it can help to better understand mechanisms of PDT and increase its efficiency and applicability.

High oxygen partial pressure increases photodynamic effect on HeLa cell lines in the presence of chloraluminium phthalocyanine.

BACKGROUND: Photodynamic therapy (PDT) is linked with oxidative damage of biomolecules causing significant impairment of essential cellular functions that lead to cell death. It is the reason why photodynamic therapy has found application in treatment of different oncological, cardiovascular, skin and eye diseases. Efficacy of PDT depends on combined action of three components; sensitizer, light and oxygen. In the present study, we examined whether higher partial pressure of oxygen increases lethality in HeLa cell lines exposed to light in the presence of chloraluminium phthalocyanine disulfonate (ClAlPcS2). METHODS: ClAlPcS2- sensitized HeLa cells incubated under different oxygen conditions were exposed to PDT. Production of singlet oxygen ((1)O2) and other forms of reactive oxygen species (ROS) as well as changes in mitochondrial membrane potential were determined by appropriately sensitive fluorescence probes. The effect of PDT on HeLa cell viability under different oxygen conditions was quantified using the standard methylthiazol tetrazolium (MTT) test. RESULTS: At the highest oxygen concentration of 28 ± 2 mg/l HeLa cells were significantly more sensitive to light-activated ClAlPcS2 (EC50=0.29 ± 0.05 µM) in comparison to cells incubated at lower oxygen concentrations of 8 ± 0.5 and 0.5 ± 0.1 mg/l, where the half maximal effective concentration was 0.42 ± 0.06 µM and 0.94 ± 0.14 µM, respectively. Moreover, we found that the higher presence of oxygen is accompanied with higher production of singlet oxygen, a higher rate of type II photodynamic reactions, and a significant drop in the mitochondrial membrane potential. CONCLUSION: These results demonstrate that the photodynamic effect in cervical cancer cells utilizing ClAlPcS2 significantly depends on oxygen level.

Study of photodynamic effects on NIH 3T3 cell line and bacteria.

BACKGROUND: Bacterial resistance to antibiotics is a constantly growing challenge. Photodynamic therapy (PDT) offers a new approach to the treatment of bacterial and viral diseases. The aim of this study was to compare the efficacy of photosensitizers used in PDT applied to cell lines and bacterial strains. METHODS: We tested the cytotoxicity and phototoxicity of 3 photosensitizers: TPPS4, ZnTPPS4 and TMPyP applied to the NIH3T3 cell line using two established methods for measuring ROS production and, MTT viability assay. Bacterial viability was determined spectrophotometrically over 24 h following PDT. RESULTS: The most efficient photosensitiser was TMPyP as it reduced the viability of the NIH3T3 cell line by more than 85%. In general, the photosensitisers were more phototoxic to the two Gram-positive bacterial strains, Enterococcus faecalis and Staphylococcus aureus. The viability of E. faecalis was reduced to 78 % by a dose radiation 0.5 J/cm(2) and concentration of TMPyP 1.562 µmol/L. The viability of bacterium S. aureus was reduced to 23 % when exposed to a radiation dose 0.5 J/cm(2) and 100 µmol/L concentration of ZnTPPS4. The highest viability decrease (15 %) for Pseudomonas aeruginosa was caused by 0.5 J/cm(2) radiation dose and 50 µmol/L TMPyP concentration. Escherichia coli proved to be PDT resistant as the bacterial viability was higher than 90%. CONCLUSIONS: The goal of the present study was to test the efficiency of photosensitizers on the NIH 3T3 cell line and bacterial cells. Subsequently we would like to study effectiveness of photosensitizers bound to carriers (for example cyclodextrins) on other cell line and bacterial strain.

The application of antimicrobial photodynamic therapy on S. aureus and E. coli using porphyrin photosensitizers bound to cyclodextrin.

Photodynamic therapy is usually used against malignant and non-malignant tumors. Nowadays, due to resistance of bacterial strains, we are looking for a new antimicrobial strategy to destroy bacteria with minimal invasive consequences. The worldwide increase in antibiotic resistance among different classes of gram-positive and gram-negative bacteria has led to the search for alternative anti-microbial therapies such as antimicrobial PDT (aPDT). Development antimicrobial technology combines a nontoxic compound, called photosensitizer, visible light of the appropriate wavelength, and the generation of reactive oxygen species. In this work, the photosensitizers TMPyP and ZnTPPS4 are investigated for photodynamic and antimicrobial photodynamic therapy. We tested these two porphyrins on two cell lines and two bacterial strains to compare effectiveness. In addition, we applied photosensitizers bound in the complex created with hp-ß-cyclodextrin. The light-emitting diodes were used at the doses 0, 1, 5, 10 J/cm(2) for cells and 0, 150 J/cm(2) for bacteria. Tested concentrations for cells and microbes were from 0.5 to 50 µM and from 0.78 to 100 µM, respectively. From this work it can be concluded that TMPyP is a promising compound both in aPDT and in PDT, particularly in contrast to ZnTPPS4, which was efficient only in PDT. Furthermore, the eradication of gram-positive bacteria is possible only with higher concentrations of ZnTPPS4.

Photodynamic therapy for enhancing antitumour immunity.

BACKGROUND: Photodynamic therapy (PDT) is a new modality in cancer treatment. It is based on the tumour-selective accumulation of a photosensitizer followed by irradiation with light of a specific wavelength. PDT is becoming widely accepted owing to its relative specificity and selectivity along with absence of the harmful side-effects of chemo and radiotherapy. There are three known distinct mechanisms of tumour destruction following PDT, generation of reactive oxygen species which can directly kill tumour cells, tumour vascular shutdown which can independently lead to tumour destruction via lack of oxygen and nutrients and thirdly enhanced antitumour immunity. METHODS: A review based on the literature acquired from the PubMed database from 1983 with a focus on the enhanced antitumour immunity effects of PTD. RESULTS AND CONCLUSION: Tumour cell death is accompanied by the release of a large number of inflammatory mediators. These induce a non-specific inflammatory response followed by gradual adaptive antitumour immunity. Further, a combination of PDT with the immunological approach has the potential to improve PDT efficiency and increase the cure rate. This short review covers specific methods for achieving these goals.

Study of the photodynamic effect on the A549 cell line by atomic force microscopy and the influence of green tea extract on the production of reactive oxygen species.

We studied the morphology of the A549 cell line (human lung carcinoma cells) before and after photodynamic therapy (PDT) by atomic force microscopy. PDT was induced by an efficient light-emitting diode source with total light dose of 15 J cm(-2) in the presence of the sensitizer zinc-5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrine. In the presence of molecular oxygen, light activation of the photosensitizer, which accumulates in cancer cells, leads to the local production of reactive oxygen species (ROS). This is one of several reasons leading to cell death, and in some cases we could observe signs of apoptosis. We detected the kinetics of ROS production to be dependent on the presence of green tea extract.

Photodynamic and sonodynamic treatment by phthalocyanine on cancer cell lines.

Photodynamic therapy is a modality of treatment for tumors. The photochemical interactions of sensitizer, light and molecular oxygen produce reactive oxygen species (ROS) such as singlet oxygen, peroxide, hydroxyl radical and superoxide ion. The tumor is destroyed either by the formation of highly reactive singlet oxygen (type II mechanism) or by the formation of radical products (type 1 mechanism) generated in an energy transfer reaction. The resulting damage to organelles within malignant cells leads to tumor ablation. The cellular effects include membrane damage, mitochondrial damage and DNA damage. A new treatment modality called sonodynamic therapy has been developed, in which the ultrasound-induced cytotoxicity of sonochemical sensitizers inhibits tumor growth. In this study, the promising new generation of sensitizers - phthalocyanines - were used to induce the photodamage. In addition, we applied an ultrasound treatment to support the photodynamic effect. We report on the production of ROS in G361 melanoma cells. Light-emitting diodes were used to evoke the photodynamic effect. Changes in cells were evaluated using fluorescence microscope and atomic force microscopy. The quantitative ROS production changes in relation to sensitizer concentration, irradiation doses and ultrasound intensity were proved by a fluororeader. Our results showed the highest generation of ROS within G361 melanoma cells was achieved at an irradiation dose of 15 Jcm(-2) followed by ultrasound treatment at intensity of 2 Wcm(-2) and frequency of 1 MHz in the presence of 100 muM chloroaluminum phthalocyanine disulfonate (ClAlPcS2). These results suggest that ClAlPcS2 is a potential photosensitizer and sonosensitizer for sonodynamic or photodynamic treatment of cancer.

Spectral characteristics of the supramolecular complexes of polypyrrolic sensitizers and cyclodextrin carriers: usage in photodynamic therapy of tumors.

The objective of our work was to describe the photophysical properties (absorption and fluorescence) of the sensitizers TPPS4, ZnTPPS4 a PdTPPS4 and above all the complexes of these sensitizers with cyclodextrin carriers HP-alpha-CD, HP-beta-CD and HP-gamma-CD (2-hydroxypropyl-alpha, beta, gamma-cyclodextrin) in a suitable environment for the cultivation of cancerous cell lines, and to determine the optimal radioactive conditions for maximizing photodynamic effects in cancerous cells.

The cellular uptake of sensitizers bound to cyclodextrin carriers.

Photodynamic therapy of cancer uses the interaction of sensitizers and light to destroy cancer cells. In this study we tested the cellular uptake of meso-tetrakis(4-sulfonatophenyl)porphine (TPPS4) and its complex PdTPPS4 in the presence or absence of 2-hydroxypropyl-cyclodextrins (hpCDs) on G361 human melanoma cells. Self-fluorescence in G361 cells were measured by Perkin-Elmer LS50B luminometer equipped with well plate reader accessory. Morphological changes in cells have been evaluated using inversion fluorescent microscope Olympus IX 70 and image analysis. The uptake of the sensitizer PdTPPS4 at the given time interval from 1 to 48 hours is markedly higher than the uptake of TPPS4. The highest uptake was found for sensitizer PdTPPS4 in combination with hpbetaCD. TPPS4 and PdTPPS4 especially in the supramolecular complex with nontoxic cyclodextrin carriers represent efficient sensitizers for photodynamic therapy in vitro on G361 cells.