ABSTRACT
Monitoring water quality in reservoirs is essential for the maintenance of aquatic ecosystems and socioeconomic services. In this scenario, the observation of abrupt elevations of physicochemical parameters, such as turbidity and other indicators, can signal anomalies associated with the occurrence of critical events, requiring operational actions and planning to mitigate negative environmental impacts on water resources. This work aims to integrate Machine Learning methods specialized in anomaly detection with data obtained from remote sensing images to identify with high turbidity events in the surface water of the Três Marias Hydroelectric Reservoir. Four distinct threshold-based scenarios were evaluated, in which the overall performance, based on F1-score, showed decreasing trends as the thresholds became more restrictive. In general, the anomaly identification maps generated through the models ratified the applicability of the methods in the diagnosis of surface water in reservoirs in distinct hydrological contexts (dry and wet), effectively identifying locations with anomalous turbidity values.
ABSTRACT
PURPOSES: The aim of the study was to assess the efficacy of a treatment protocol that combines photodynamic therapy (PDT) and nitroglycerin (NG) on human retinoblastoma tumors xenografted on mice. We aimed to increase the PDT efficiency (in our least treatment-responsive retinoblastoma line) with better PS delivery to the tumor generated by NG, which is known to dilate vessels and enhance the permeability and retention of macromolecules in solid tumors. METHODS: In vivo follow-up of the therapeutic effects was performed by sodium MRI, which directly monitors variations in sodium concentrations non-invasively and can be used to track the tumor response to therapy. NG ointment was applied one hour before PDT. The PDT protocol involves double-tumor targeting, i.e., cellular and vascular. The first PS dose was injected followed by a second one, separated by a 3 h interval. The timelapse allowed the PS molecules to penetrate tumor cells. Ten minutes after the second dose, the PS was red-light-activated. RESULTS: In this study, we observed that the PDT effect was enhanced by applying nitroglycerin ointment to the tumor-bearing animal's skin. PDT initiates the bystander effect on retinoblastomas, and NG increases this effect by increasing the intratumoral concentration of PS, which induces a higher production of ROS in the illuminated region and thus increases the propagation of the cell death signal deeper into the tumor (bystander effect).
ABSTRACT
Fourier Transform Infrared (FTIR) microspectroscopy was used to highlight the interactions between two photosensitisers (PS) of different geometries, TPPmOH4 and a glycoconjugated analogous, TPPDegMan, and lipid bilayers modelling retinoblastoma cell membranes. Retinoblastoma is a rare disease occurring in young infants, for whom conservative treatments may present harmful side-effects. Photodynamic therapy (PDT) is expected to induce less side-effects, as the photosensitiser is only activated when the tumour is illuminated. Since efficiency of the treatment relies on photosensitiser penetration in cancer cells, bilayers with three lipid compositions - pure SOPC, SOPC/SOPE/SOPS/Chol (56:23:11:10) and SOPC/SOPE/SOPS/Chol/CL (42:32:9:8:6) - were used as plasma and mitochondria model membranes. FTIR spectra showed that the interaction of the PSs with the lipid bilayers impacted the lipid organization of the latter, causing significant spectral variations. Both studied photosensitisers inserted at the level of lipid hydrophobic chains, increasing chain fluidity and disorder. This was confirmed by surface pressure measurements. Photosensitisers - TPPmOH4 more than TPPDegMan - also interacted with the polar region of the bilayer, forming hydrogen bonds with phosphate groups that induced major shifts of phosphate absorption bands. This difference in PS interaction with moieties in the polar region was more pronounced with the models with complex lipid composition.
Subject(s)
Lipid Bilayers/chemistry , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Retinal Neoplasms/radiotherapy , Retinoblastoma/radiotherapy , Antineoplastic Agents/pharmacology , Cell Membrane/chemistry , Humans , Molecular Structure , Phospholipids/chemistry , Photochemotherapy , Spectroscopy, Fourier Transform Infrared , Surface TensionABSTRACT
The proof of concept for two-photon activated photodynamic therapy has already been achieved for cancer treatment but the efficiency of this approach still heavily relies on the availability of photosensitizers combining high two-photon absorption and biocompatibility. In this line we recently reported on a series of porphyrin-triphenylamine hybrids which exhibit high singlet oxygen production quantum yield as well as high two-photon absorption cross-sections but with a very poor cellular internalization. We present herein new photosensitizers of the same porphyrin-triphenylamine hybrid series but bearing cationic charges which led to strongly enhanced water solubility and thus cellular penetration. In addition the new compounds have been found localized in mitochondria that are preferential target organelles for photodynamic therapy. Altogether the strongly improved properties of the new series combined with their specific mitochondrial localization lead to a significantly enhanced two-photon activated photodynamic therapy efficiency.
Subject(s)
Aniline Compounds/pharmacology , Mitochondria/drug effects , Photochemotherapy , Photons , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Aniline Compounds/chemistry , Cations/chemical synthesis , Cations/chemistry , Cations/pharmacology , Cell Death/drug effects , Dose-Response Relationship, Drug , HT29 Cells , Humans , Molecular Structure , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/chemistry , Porphyrins/chemistry , Structure-Activity Relationship , Tumor Cells, CulturedABSTRACT
Porphyrin- or phthalocyanine-bridged silsesquioxane nanoparticles (BSPOR and BSPHT) were prepared. Their endocytosis in MCF-7 cancer cells was shown with two-photon excited fluorescence (TPEF) imaging. With two-photon excited photodynamic therapy (TPE-PDT), BSPOR was more phototoxic than BSPHT, which in contrast displayed a very high signal for photoacoustic imaging in mice.
ABSTRACT
Non-point source water pollution is a major problem in most parts of the world, but is also very difficult to quantify and control since it is not easily separated from point sources and can theoretically originate from the whole watershed. In this article, we evaluate the relationship between land use and land cover and four water pollution parameters in a watershed in Southeast Brazil. The four parameters are nitrate, total ammonia nitrogen, total phosphorous, and dissolved oxygen. To help concentrate on non-point source pollution, only data from the wet seasons of the time period (2001-2013) were analysed, based on the fact that precipitation causes runoff which is the main cause of diffuse pollution. The parameters measured were transformed into loads, which were in turn associated with an exclusive contribution area, so that every measuring station could be considered independent. Analyses were also performed on riparian zones of different widths to verify if the effect of the land cover on the water quality of the stream decreases with the increased distance. Pearson correlation coefficients indicate that urban areas and agriculture/pasture tend to worsen water quality (source). Conversely, forest and riparian areas have a reducing effect on pollution (sink). The best results were obtained for total ammonia nitrogen and dissolved oxygen using the whole exclusive contribution areas with determination coefficients better than R (2)≈0.8. Nitrate and total phosphorous did not produce valid models. We suspect that the transformation delay from total ammonia nitrogen to nitrate might be an important factor for the poor result for this parameter. For phosphorous, we think that the phosphorous sink in the bottom sediment might be the most limiting factor explaining the failure of our models.
Subject(s)
Models, Theoretical , Rivers/chemistry , Water Pollutants, Chemical/analysis , Agriculture , Ammonia/analysis , Brazil , Environmental Monitoring/methods , Forests , Nitrates/analysis , Oxygen/analysis , Phosphorus/analysis , Urbanization , Water Pollution/analysisABSTRACT
A novel non-toxic porous silicon nanoparticle grafted with a mannose-6-phosphate analogue and applicable in 2-photon imaging and photodynamic therapy was specifically designed for targeting prostate cancer cells.
ABSTRACT
Biodegradable bridged silsesquioxane (BS) nanomaterials for two-photon-excited (TPE) imaging and therapy of breast cancer cells were described. A versatile synthesis was developed to design monodisperse tetra-alkoxysilylated diamino-diphenylbutadiene or Zn-porphyrin-based nanospheres of 30 to 50 nm.
Subject(s)
Disulfides/chemistry , Microscopy, Fluorescence, Multiphoton/methods , Nanoparticles/metabolism , Nanoparticles/therapeutic use , Organosilicon Compounds/chemical synthesis , Organosilicon Compounds/therapeutic use , Cell Survival/drug effects , Dose-Response Relationship, Drug , Humans , MCF-7 Cells , Molecular Structure , Nanoparticles/chemistry , Organosilicon Compounds/metabolism , Particle Size , Photosensitizing Agents/chemical synthesis , Photosensitizing Agents/metabolism , Photosensitizing Agents/therapeutic use , Structure-Activity Relationship , Surface PropertiesABSTRACT
The development of personalized and non-invasive cancer therapies based on new targets combined with nanodevices is a major challenge in nanomedicine. In this work, the over-expression of a membrane lectin, the cation-independent mannose 6-phosphate receptor (M6PR), was specifically demonstrated in prostate cancer cell lines and tissues. To efficiently target this lectin a mannose-6-phosphate analogue was synthesized in six steps and grafted onto the surface of functionalized mesoporous silica nanoparticles (MSNs). These MSNs were used for inâ vitro and exâ vivo photodynamic therapy to treat prostate cancer cell lines and primary cell cultures prepared from patient biopsies. The results demonstrated the efficiency of M6PR targeting for prostate cancer theranostic.
Subject(s)
Biomarkers, Tumor/antagonists & inhibitors , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/drug therapy , Receptor, IGF Type 2/antagonists & inhibitors , Biomarkers, Tumor/genetics , Cell Line, Tumor , Humans , Male , Mannosephosphates/chemical synthesis , Mannosephosphates/chemistry , Nanoparticles/chemistry , Nanoparticles/therapeutic use , Particle Size , Photochemotherapy , Porosity , Prostatic Neoplasms/genetics , Prostatic Neoplasms/pathology , Receptor, IGF Type 2/genetics , Silicon Dioxide/chemistry , Surface PropertiesABSTRACT
BACKGROUND: PDT represents a very localized and non-mutagen antitumoral treatment using a photosensitive molecule (porphyrin family) light activated. The first way of cell damage is a direct one, active on the very site where ROSs have been produced. The second one is indirect by activating and transmitting the processes of cellular death signaling. In order to seek for a better characterization of the photo-biology involved in in vivo PDT and to better understand the differences on the treatment outcome, we have used three different human retinoblastomas xenografted on mice. METHODS: Mice were treated according to the double targeting protocol exposed in a previous paper. One i.v. dose (0.6 mg/kg) of PS was followed by a second dose, separated by a 3 h interval (double targeting PDT). As a consequence both cancer cells and blood vessels were targeted. The treatment was repeated two times, at 4 days interval. RESULTS: First of all, sodium MRI revealed qualitative differences in the sodium average content of the three retinoblastoma lines before treatment. After the PDT treatments the tumor responses were different between the lines as revealed by sodium MRI and later on by histology. CONCLUSIONS: We have put into evidence that PDT is accompanied by a bystander effect that may propagate the cellular death triggered by the initial photoreaction. This effect is highly dependent on the cellular density of the tissue; therefore this factor is to be taken into account in clinical PDT protocols.
Subject(s)
Cell Death/drug effects , Neovascularization, Pathologic/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Retinoblastoma/drug therapy , Animals , Cell Count , Cell Line, Tumor , Humans , Magnetic Resonance Imaging , Mice , Mice, Nude , Reactive Oxygen Species/metabolismABSTRACT
Hemoprotein mimics, cobalt picket fence porphyrins have been prepared in the gas phase as neutral molecules for the first time. Their ligation properties have been studied with 1-methylimidazole and compared with those of other cobalt porphyrins, tetraphenyl porphyrin, and cobalt protoporphyrin IX chloride, in view of studying the sterical properties of the ligation. It is shown that the cobalt picket fence porphyrin can only accept one 1-methylimidazole ligand in contrast to less sterically crowded porphyrins like cobalt tetraphenylporphyrin that present two accessible ligation sites. The femtosecond dynamics of these ligated systems have been studied after excitation at 400 nm, in comparison with the unligated ones. The observed transients are formed in much shorter times, 30 fs for the ligated species, as compared to free species (100 fs), supporting the porphyrin to metal charge transfer nature of these transients. The similar decays of the ligated transients <1 ps reveal the absence of photodissociation of the cobalt-1-methylimidazole bond at this step of evolution.
Subject(s)
Gases/chemistry , Hemeproteins/chemistry , Imidazoles/chemistry , Protoporphyrins/chemistry , Molecular StructureABSTRACT
Porous silicon nanoparticles (pSiNPs) act as a sensitizer for the 2-photon excitation of a pendant porphyrin using NIR laser light, for imaging and photodynamic therapy. Mannose-functionalized pSiNPs can be vectorized to MCF-7 human breast cancer cells through a mannose receptor-mediated endocytosis mechanism to provide a 3-fold enhancement of the 2-photon PDT effect.
Subject(s)
Nanoparticles/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/therapeutic use , Porphyrins/therapeutic use , Silicon/therapeutic use , Biocompatible Materials/chemistry , Biocompatible Materials/therapeutic use , Cell Death/drug effects , Cell Death/radiation effects , Endocytosis/drug effects , Endocytosis/radiation effects , Humans , Infrared Rays , MCF-7 Cells , Mannose/chemistry , Mannose/therapeutic use , Microscopy, Confocal , Microscopy, Fluorescence , Nanoparticles/chemistry , Photons , Photosensitizing Agents/chemistry , Porosity , Porphyrins/chemistry , Silicon/chemistryABSTRACT
We report the properties of glycoconjugated porphyrin dimers behaving as highly sensitive ratiometric temperature sensors in water. This effect results from interactions between carbohydrate and water altering molecular relaxation kinetics leading to temperature sensitive dual emission. These dimers are robust ratiometric fluorescent probes over a large temperature window (20-90 °C).
Subject(s)
Dimerization , Glycoconjugates/chemistry , Porphyrins/chemistry , TemperatureABSTRACT
In order to avoid side effects at the time of cancer eradication to the patients, the selectivity of treatments has become of strategic importance. In the case of photodynamic therapy (PDT), two-photon absorption combined with active targeting of tumors could allow both spatial and chemical selectivity. In this context, we present the synthesis, spectroscopic, and biological properties of a series of porphyrin-triphenylamine hybrids with excellent singlet oxygen production capacities and good two-photon absorption.
Subject(s)
Aniline Compounds/chemical synthesis , Colonic Neoplasms/chemistry , Colonic Neoplasms/drug therapy , Glycoconjugates/chemical synthesis , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use , Porphyrins/chemical synthesis , Singlet Oxygen/chemistry , Aniline Compounds/chemistry , Biological Evolution , Cell Line, Tumor , Dimerization , Glycoconjugates/chemistry , Humans , Photochemotherapy , Photons/therapeutic use , Porphyrins/chemistry , Spectrum AnalysisABSTRACT
Non-toxic porous silicon nanoparticles carry porphyrin covalently attached to their surface inside breast cancer cells for a more efficient photodynamic effect.
Subject(s)
Nanoparticles/chemistry , Porphyrins/chemistry , Silicon/chemistry , Anions/chemistry , Breast Neoplasms/drug therapy , Female , Humans , MCF-7 Cells , Photochemotherapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/therapeutic use , PorosityABSTRACT
In the course of a Photodynamic Therapy (PDT) protocol, disaggregation of the sensitizer upon binding to plasma proteins and lipoproteins is one of the first steps following intravenous administration. This step governs its subsequent biodistribution and has even been evoked as possibly orientating mechanism of tumor destruction. It is currently admitted as being mainly dependent on sensitizer's hydrophobicity. In this context, as far as glycoconjugation of meso-tetraphenylporphyrin (TPP) macrocycle, a promising strategy to improve targeting of retinoblastoma cells confers to the sensitizer an amphiphilic character, we have studied the effect of this strategy on binding to plasma proteins and lipoproteins. With the exception of the majoritary protein binding (more than 80%) of more hydrophilic para-tetraglycoconjugated derivatives, high density lipoproteins (HDL) appear as main plasma carriers of the other amphiphilic glycoconjugated photosensitizers. This HDL-binding is a combined result of binding affinities (logKa ranging from 4.90 to 8.77 depending on the carrier and the TPP derivative considered) and relative plasma concentrations of the different carriers. Evaluation of binding affinities shows that if hydrophobicity can account for LDL- and HDL-affinities, it is not the case for albumin-affinity. Molecular docking simulations show that, if interactions are mainly of hydrophobic nature, polar interactions such as hydrogen bonds are also involved. This combination of interaction modalities should account for the absence of clear relationship between albumin-affinity and hydrophobicity. Taken together, our findings clarify the importance, but also the limits, of hydrophobicity's role in structure-plasma distribution relationship.
Subject(s)
Blood Proteins/metabolism , Porphyrins/metabolism , Drug Carriers/metabolism , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Lipoproteins/metabolism , Photochemotherapy/methods , Photosensitizing Agents/metabolism , Protein Binding/physiology , Retinoblastoma , Serum Albumin/metabolism , Tissue Distribution/physiologyABSTRACT
We report the synthesis of bioconjugated zinc porphyrin dimers 1a-e designed as photosensitizers for one-photon and two-photon excited photodynamic therapy. These macrocycles are substituted with carbohydrate units (glucose, mannose, lactose) in order to target tumor cells over-expressing lectin membrane receptors. Polarity, singlet oxygen production and in vitro photocytotoxicity are studied to determine their photodynamic therapy potentiality.
Subject(s)
Glycoconjugates/chemistry , Glycoconjugates/pharmacology , Metalloporphyrins/chemistry , Metalloporphyrins/pharmacology , Neoplasms/drug therapy , Photosensitizing Agents/chemistry , Photosensitizing Agents/pharmacology , Cell Line, Tumor , Dimerization , Glucose/chemistry , Glucose/pharmacokinetics , Glucose/pharmacology , Glycoconjugates/pharmacokinetics , Humans , Lactose/chemistry , Lactose/pharmacokinetics , Lactose/pharmacology , Mannose/chemistry , Mannose/pharmacokinetics , Mannose/pharmacology , Metalloporphyrins/pharmacokinetics , Neoplasms/metabolism , Photochemotherapy , Photosensitizing Agents/pharmacokinetics , Singlet Oxygen/metabolismABSTRACT
BACKGROUND: Previous in vivo studies on photodynamic therapy (PDT)-treated, high cellular density tumors showed evidences of a bystander effect accompanying the therapy, cellular death continuing beyond the limits of the photochemical reactions in time and space. This process is generated by the initially damaged cells on the light pathway. The aim of this study was to determine if the bystander effect may be induced as well in colorectal xenografted tumors (less compact structure) and if the cellular signaling depends primarily on cellular proximity or not. METHODS: The photosensitizer was a glycoconjugated, meso substituted porphyrin derivative synthesized at Institut Curie. The longitudinal follow-up of the tumors was carried out by (23)Na/(1)H MRI, ideal imaging modality for mapping the extracellular compartment. Two regimens were followed in order to target either blood vessels alone or blood vessels and cancer cells simultaneously. RESULTS: The antivascular PDT did not succeed to arrest the tumors growth at the end of the follow-up. For double targeting PDT, we managed to stop the tumoral evolution. Sodium MRI evidenced a bystander effect. CONCLUSION: The results obtained showed that the bystander effect is more difficult to induce for the type of colorectal tumors used in this work. It needs a double treatment, 4 days apart, in order to be promoted.
Subject(s)
Bystander Effect/drug effects , Colorectal Neoplasms/drug therapy , Photochemotherapy/methods , Photosensitizing Agents/pharmacology , Porphyrins/pharmacology , Animals , Apoptosis/drug effects , Cell Count , Diffusion Magnetic Resonance Imaging , Female , Mice , Mice, Nude , Xenograft Model Antitumor AssaysABSTRACT
Mesoporous silica nanoparticles (MSN) for photodynamic therapy (PDT) were coated with poly-(L-lysine) and hyaluronic acid (HA) by using the layer-by-layer method. HA is able to target cancer cells over-expressing the corresponding CD44 receptor. MSN functionalized with HA (MSN-HA) were more efficient than MSN without the targeting moiety when PDT was performed at low fluence (14 Jcm(-2)) and low dosage of MSN (20 µgmL(-1)) on HCT 116 colorectal cancer cells, known to over-express the CD44 receptor. Incubation of HCT-116 cancer cells with an excess of HA impaired the PDT effect with MSN-HA thus demonstrating that an active endocytosis mechanism was involved in the uptake of MSN-HA by these cells.
Subject(s)
Apoptosis/drug effects , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/pathology , Hyaluronic Acid/administration & dosage , Nanocapsules/chemistry , Photochemotherapy/methods , Silicon Dioxide/chemistry , Cell Line, Tumor , Humans , Hyaluronic Acid/chemistry , Nanocapsules/administration & dosage , Porosity , Treatment OutcomeABSTRACT
Glycodendrimeric porphyrins seem promising photosensitizers usable in photodynamic therapy. Evidence of their ability to interact with an artificial supported bilayer membrane exhibiting a model sugar receptor has been previously shown. In the present work, the interaction of the glycodendrimeric porphyrins with retinoblastoma cells bearing the actual sugar receptor has been assessed by both classical cell cultures and an original approach using the quartz crystal microbalance (QCM-D). Our results showed that unlike cell cultures, QCM-D allowed analyzing the mechanism of interaction of the glycodendrimeric porphyrins with the sugar receptor. Not only was molecular recognition demonstrated, but our methodology also proved efficient to discriminate between the studied compounds, depending on the presence of carbohydrate, and the spacer length.