scholarly journals Primary screening of substances-photosensibilizers of the bacteriochlorin range for photodynamic therapy of malignant neoplasms

2018 ◽  
Vol 64 (3) ◽  
pp. 283-289 ◽  
Author(s):  
E.A. Plotnikova ◽  
M.A. Grin ◽  
P.V. Ostroverkhov ◽  
I.V. Pantushenko ◽  
R.I. Yakubovskaya ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Malignant Tumors ◽  
Light Exposure ◽  
Spectral Characteristics ◽  
Red Light ◽  
Wavelength Region ◽  
Biological Properties ◽  
Malignant Neoplasms ◽  
Long Wavelength ◽  
Primary Screening

This paper presents a primary screening of bacteriochlorin-type compounds with aminoamide, propyl and carbohydrate substituents aimed for development a new generation photosensitizers (PS) for photodynamic therapy of malignant tumors. Absorption and fluorescence spectral characteristics of the compounds, their storage stability in solutions under dark conditions and light exposure, photo-induced and dark cytotoxicity against human HEp2 tumor cells have been studied. It has been shown that the dyes with aminoamide substituents have an absorbtion maximum at 754±2 nm in the long wavelength region and they are not stable during storage (the specific fluorescence intensity decreased by 33-56% during 24 hours). The long wavelength region absorption of the propyl and carbohydrate substituted compounds varied in the range 780-831 nm, they were stable in solutions during storage and under light irradiation. Except the dye with a carbohydrate residue in the exocycle E, all PS exhibited the high photo-induced activity and low level of the dark cytotoxicity. The highest photo-induced cytotoxicity was observed for compounds with aminoamide substituents inthe macrocyclic ring (IC 50 values ranged from 17 nM to49 nM after 2 hour incubation with PS followed by exposure to the 10 J/cm 2 dose of red light). Taking into account the totality of the physico-chemical and biological properties, as well as manufacturability of production, O-propyloxime-N-propoxybacteriopurinimide methyl ester was chosen as the most promising candidate compound for further investigations.

scholarly journals Photodynamic therapy of cancer of large duodenal papilla and extrahepatic bile ducts

2020 ◽  
Vol 9 (2) ◽  
pp. 18-28
Author(s):  
E. F. Stranadko ◽  
A. V. Baranov ◽  
V. A. Duvansky ◽  
A. I. Lobakov ◽  
V. A. Morokhotov ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Bile Ducts ◽  
Malignant Tumors ◽  
Control Group ◽  
Malignant Neoplasms ◽  
Duodenal Papilla ◽  
Risk Of Death ◽  
Photodynamic Therapy Of Cancer ◽  
Bile Drainage ◽  
Extrahepatic Bile Ducts

The problem of treating patients with malignant neoplasms of the extrahepatic bile ducts and the large duodenal papilla remains relevant due to the growing incidence, high mortality, and a pronounced decrease in the quality of life of patients, despite the radical surgery. The purpose of this study was to evaluate the effectiveness of photodynamic therapy (PDT) in inoperable patients with malignant tumors of these localizations.The study is based on the treatment of 79 patients with adenocarcinoma of large duodenal papilla and extrahepatic bile ducts. 29 patients received palliative bile drainage operations with PDT. 50 patients in the control group only had palliative bile drainage operations. Patients in the study group received from 1 to 3 PDT courses in a year. In total, 29 patients received 52 PDT courses. The tolerance to the method and the life expectancy of patients were evaluated. The median survival of patients who underwent PDT was 18 months (11–60 months); in the control group – 11.5 months. PDT, in combination with bile drainage operation, is an effective method for the treatment of inoperable patients with malignant neoplasms of the extrahepatic bile ducts and the large duodenal papilla in the absence of severe complications and with easy tolerance to therapy by patients. For the treatment and prolongation of life of patients whose radical surgical treatment is associated with a high risk of death, PDT seems to be the best treatment option. Results of PDT treatment for cancer of this localization are comparable with the results of radical surgeries and exceed those for palliative surgeries.

scholarly journals Possibilities of photodynamic therapy in the treatment of malignant tumors of the oral cavity

2021 ◽  
Vol 10 (3) ◽  
pp. 32-38
Author(s):  
Y. A. Panaseykin ◽  
E. V. Filonenko ◽  
F. E. Sevrukov ◽  
V. V. Polkin ◽  
P. A. Isaev ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Oral Cavity ◽  
Oral Mucosa ◽  
Surface Defects ◽  
Radiation Treatment ◽  
Malignant Tumors ◽  
Survival Rates ◽  
Functional Results ◽  
Malignant Neoplasms ◽  
Common Disease

Oral mucosa cancer is a common disease with relatively low survival rates. The standard for the treatment of malignant neoplasms (MNO) of the oral mucosa is the surgical method, chemotherapy and / or radiation therapy. With the introduction of modern protocols and the improvement of current treatment methods, the increase in survival is insignificant due to the development of local and distant relapses, the appearance of simultaneous tumors of the oral cavity. Cosmetic and functional results in patients who have undergone complex treatment for oral cancer are often unsatisfactory. There is an obvious need to develop new approaches to treating patients with cancer of the oral mucosa. Photodynamic therapy (PDT) has similar properties. With the development of endoscopic and fiber-optic equipment, the fields of PDT application have significantly expanded. Foci in the oral cavity and oropharynx became available for PDT. The early stages of oral mucosal cancer are optimal for PDT because large surface defects can be treated with minimal complications. Preservation of subepithelial and collagen structures, which is typical for PDT, promotes healing without the formation of scar processes, thereby achieving an ideal cosmetic and functional effect. The use of PDT in the treatment of oral cavity cancer is not limited only to the initial stages in an independent version. It is possible to use PDT in combination with surgical and radiation treatment. In case of massive tumor processes, PDT is used for palliative purposes. The influence of the adaptive immune response under the influence of PDT is being studied.

Primary Screening of Photosensitizers of the Bacteriochlorin Series for Photodynamic Therapy of Malignant Neoplasms

2018 ◽  
Vol 12 (3) ◽  
pp. 275-282 ◽  
Author(s):  
E. A. Plotnikova ◽  
M. A. Grin ◽  
P. V. Ostroverkhov ◽  
I. V. Pantushenko ◽  
R. I. Yakubovskaya ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Malignant Neoplasms ◽  
Primary Screening

Photodynamic Therapy for Head and Neck Cancer Xenografts in Athymic Mice

1986 ◽  
Vol 95 (5) ◽  
pp. 602-606 ◽  
Author(s):  
James H. Hill ◽  
Randall L. Plant ◽  
David M. Harris ◽  
Randal C. Paniello
Keyword(s):  
Photodynamic Therapy ◽  
Light Intensity ◽  
Head And Neck ◽  
Treatment Time ◽  
Light Exposure ◽  
Red Light ◽  
Human Head ◽  
Athymic Mice ◽  
Squamous Cancer ◽  
Argon Dye Laser

This study examines efficacy and optimal treatment variables of photodynamic therapy (PDT) for human head and neck squamous cancer (HNSC) xenografts in athymic mice. Two and four days after injection of hematoporphyrin derivative (HPD), tumors were illuminated with red light from an argon-dye laser. Sixty-three tumors were treated. With HPD dose and light intensity constant at 7.5 mg/kg and 100 mW/cm2, respectively, the extent of tumor necrosis was strongly dependent on duration of light exposure. There was no substantial difference in results for 30- and 60-minute treatment durations between animals injected with HPD 2 and 4 days before treatment. After 30 minutes treatment time, responses were seen in 8 of 10 mice (2 days post-HPD) and 11 of 12 mice (4 days post-HPD). After 60 minutes treatment time, toxicity was high. We conclude that, in this model, PDT is effective in selective killing of HNSC. For future comparison studies in this model, if the indicated HPD dose and light intensity are used we recommend a 2-day delay after HPD injection and a light exposure duration of 30 minutes

scholarly journals Photodynamic Therapy for Acinetobacter baumannii Burn Infections in Mice

2009 ◽  
Vol 53 (9) ◽  
pp. 3929-3934 ◽  
Author(s):  
Tianhong Dai ◽  
George P. Tegos ◽  
Zongshun Lu ◽  
Liyi Huang ◽  
Timur Zhiyentayev ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Acinetobacter Baumannii ◽  
Light Exposure ◽  
Middle Eastern ◽  
Red Light ◽  
Dorsal Surface ◽  
Multidrug Resistant ◽  
Dependent Manner ◽  
Chronic Infections ◽  
Bacterial Luminescence

ABSTRACT Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 108 A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections.

Photodynamic Therapy with 5-Aminolevulinic Acid Induces Apoptosis and Caspase Activation in Malignant T Cells

2001 ◽  
Vol 5 (1) ◽  
pp. 8-13 ◽  
Author(s):  
Faten Gad ◽  
Gilles Viau ◽  
Michele Bousbira ◽  
Richard Bertrand ◽  
Robert Bissonnette
Keyword(s):  
Photodynamic Therapy ◽  
Dna Fragmentation ◽  
Caspase 3 ◽  
Aminolevulinic Acid ◽  
Light Exposure ◽  
Red Light ◽  
Jurkat Cells ◽  
Caspase Activation ◽  
Light Fluence ◽  
Malignant T Cells

Background: Preliminary studies have suggested that photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) can improve psoriasis and mycosis fungoides, two diseases where normal or malignant T cells play a central role. Objectives: To determine if ALA-PDT induces apoptosis and caspase activation in Jurkat cells, a malignant T-cell line. Methods: Jurkat cells were incubated with ALA in the presence of [14C]-thymidine followed by red light exposure. DNA fragmentation was measured 24 hours later with a DNA elution assay. The influence on DNA fragmentation of ALA concentration, time between ALA addition and light exposure, as well as light fluence were studied. The occurrence of oligonucleosome-sized DNA fragmentation was also studied with DNA electrophoresis. Caspase-3-like activity was monitored by measuring Ac-DEVD-AMC hydrolysis. Results: DNA fragmentation as high as 88% was observed 24 hours after ALA-PDT. The percentage of DNA fragmentation increased with increasing doses of ALA, red light fluence, as well as longer incubation time with ALA. DNA fragmentation was observed as early as 3 hours after ALA-PDT. The presence of apoptosis after ALA-PDT was confirmed by DNA electrophoresis. An increase in caspase-3-like activities was detected following ALA-PDT. Conclusion: ALA-PDT induces apoptosis and caspase-3-like activation in Jurkat cells.

Simple red light sources for photodynamic therapy of malignant tumors

1994 ◽  
Author(s):  
K. S. Low ◽  
H. K. Chan ◽  
A. S. Haji Baba ◽  
C. H. Yip ◽  
K. W. Chang ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Malignant Tumors ◽  
Red Light ◽  
Light Sources

scholarly journals Rationally Designed Long-Wavelength Absorbing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy

2019 ◽  
Author(s):  
Johannes Karges ◽  
Franz Heinemann ◽  
Marta Jakubaszek ◽  
Federica Maschietto ◽  
Chloé Subecz ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Water Solubility ◽  
Clinical Success ◽  
Biological Properties ◽  
The Body ◽  
Multicellular Tumor Spheroids ◽  
Spectral Window ◽  
Long Wavelength ◽  
Polypyridine Complexes ◽  
Nanomolar Range

The utilization of Photodynamic Therapy (PDT) for the treatment of various types of cancer has gained increasing attention over the last decades. Despite the clinical success of approved photosensitizers (PSs), their application is limited due to poor water solubility, aggregation, photodegradation, and slow clearance from the body. To overcome these drawbacks, research efforts are devoted towards the development of metal complexes and especially Ru(II) polypyridine complexes based on their attractive photophysical and biological properties. Despite the recent research developments, the vast majority of complexes utilize blue or UV-A light to obtain a PDT effect, limiting the penetration depth inside the tissue and therefore, the possibility to treat deep-seated or large tumors. To circumvent these drawbacks, we present the first example of the DFT guided search for efficient PDT PSs with a substantial spectral red shift towards the biological spectral window. Thanks to this design, we have unveiled a Ru(II) polypyridine complex, which causes phototoxicity in the very-low micromolar-to-nanomolar range at clinically relevant 595 nm, in monolayer cells as well as in 3D multicellular tumor spheroids.<br>

MECHANISMS OF IMMUNOCORRECTIVE ACTION OF PHOTODYNAMIC THERAPY AND EXOSOMES OF MESENCHYMAL STEM CELLS IN PATIENTS WITH CHRONIC WOUNDS OF THE LOWER EXTREMITIES OF DIFFERENT GENESIS

2021 ◽  
pp. 20-27
Author(s):  
O. M. Klimova ◽  
Yu. V. Ivanova ◽  
K. A. Bychenko ◽  
O. S. Merezhko ◽  
V. O. Prasol ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Growth Factor ◽  
Chronic Wounds ◽  
Light Exposure ◽  
Red Light ◽  
Lower Extremities ◽  
Light Therapy ◽  
Vascular Growth ◽  
Low Intensity ◽  
Vascular Growth Factor

Summary. Introduction. The treaonic wounds of the lower extremities today requires long-term use of antibiotic therapy, which aggravates the course of the wound process. In this regard, the search for new methods of treatment is underway. Low-intensity light exposure of various wavelengths of photodynamic therapy with photosensitizer photosensitizer Dimegin was used as a physical method, and multipotent mesenchymal-stromal cells and their exometabolites in exosomes form were used as a biological method. The aim was to study the change of barrier function of oxygen-independent and oxygen-dependent phagocytosis and serum levels of vascular growth factor (VEGF) in patients with chronic wounds of the lower extremities before and after the application of complex light exposure and exosomes. Materials and methods. Phagocytosis activity of neutrophils was investigated by assessing chemotaxis, adhesion and endocytosis and by determining reactive oxygen species (ROS) in oxygen-dependent phagocytosis using light and confocal microscopy. VEGF concentration was determined by ELISA. Results: after photodynamic therapy using with red light (λ=660nm), activation of oxygen-independent and oxygen-dependent phagocytosis was observed, as well as an increase in the synthesis of vascular growth factor in patients with chronic wounds of the lower extremities. After the application of green light (λ=530nm) and the application of exosomes, the normalization of immune processes was observed, which led to the acceleration of regenerative processes in the wound. Conclusions. Thus, after carrying out complex low-intensity light therapy and exosomes, it was possible to completely clear the wounds from necrosis in a short time.

scholarly journals Rationally Designed Long-Wavelength Absorbing Ru(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy

2019 ◽  
Author(s):  
Johannes Karges ◽  
Franz Heinemann ◽  
Marta Jakubaszek ◽  
Federica Maschietto ◽  
Chloé Subecz ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Water Solubility ◽  
Clinical Success ◽  
Biological Properties ◽  
The Body ◽  
Multicellular Tumor Spheroids ◽  
Spectral Window ◽  
Long Wavelength ◽  
Polypyridine Complexes ◽  
Nanomolar Range

The utilization of Photodynamic Therapy (PDT) for the treatment of various types of cancer has gained increasing attention over the last decades. Despite the clinical success of approved photosensitizers (PSs), their application is limited due to poor water solubility, aggregation, photodegradation, and slow clearance from the body. To overcome these drawbacks, research efforts are devoted towards the development of metal complexes and especially Ru(II) polypyridine complexes based on their attractive photophysical and biological properties. Despite the recent research developments, the vast majority of complexes utilize blue or UV-A light to obtain a PDT effect, limiting the penetration depth inside the tissue and therefore, the possibility to treat deep-seated or large tumors. To circumvent these drawbacks, we present the first example of the DFT guided search for efficient PDT PSs with a substantial spectral red shift towards the biological spectral window. Thanks to this design, we have unveiled a Ru(II) polypyridine complex, which causes phototoxicity in the very-low micromolar-to-nanomolar range at clinically relevant 595 nm, in monolayer cells as well as in 3D multicellular tumor spheroids.<br>

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