Abstract:Photodynamic therapy (PDT) is highly effective in treating tumors located near body surface, offering strong tumor suppression and low damage to normal tissue nearby. PDT is also effective for treating a number of other conditions. PDT not only provide a precise and selective method for the treatment of various diseases by itself, it can also be used in combination with other traditional therapies. Because PDT uses light as the unique targeting mechanism, it has simpler and more direct targeting capability tha… Show more
“…It was found by Gierszewski et al [38] that porphyrazines with eight peripheral isophtaloxyalkylsulfanyl substituents generate singlet oxygen with Φ ∆ values between 0.01 and 0.04 in DMF and that incorporating Mg 2+ ions into the Pzs improves their capability to generate single oxygen. The exchange of Mg 2+ (3,6) to Zn 2 (4, 7) in the tribenzoporphyrazine ring influenced the singlet oxygen generation quantum yield values, which increased from 0.05 (3) to 0.24 (4) and from 0.20 (6) to 0.59 (7). In Figures 7 and 8, the Q-bands of 6 and 7 demonstrate only minimal to no changes during irradiation, thus indicating their good stability during measurements.…”
Section: Singlet Oxygen Generation Studymentioning
confidence: 95%
“…Metal-free Pz derivative 5 (92 mg, 0.075 mmol), N,N-dimethylformamide (DMF, 25 mL), and zinc(II) acetate (41 mg, 0.225 mmol) were stirred in a round-bottomed flask under inert gas at 70 • C for 24 h. After that, the solvent was evaporated, and the residual blue oil was subjected to column chromatography (dichloromethane/methanol 50:1 then 20:1), leading to a cerulean blue product 6 (79 mg, 71% yield). R f = 0.71 (dichloromethane/methanol, 20:1, v/v (7) Lithium aluminum hydride (13 mg, 0.353 mmol) was suspended in tetrahydrofuran (THF) precooled to 0 • C and stirred for 30 min. Porphyrazine derivative 6 (95 mg, 0.074 mmol) was dissolved in THF (14 mL), and the solution was added dropwise to the reaction mixture over 40 min.…”
Section: Synthetic Proceduresmentioning
confidence: 99%
“…The absorption of light in the range of 650-850 nm, which is often described as the phototherapeutic window, as well as the generation of reactive oxygen species in the photodynamic reaction, make Pzs especially relevant for medical applications, in particular photodynamic therapy (PDT) [6]. The PDT principle is based on the photodynamic reaction, which starts from the exposure of the photosensitizer to light of an appropriate wavelength [7]. Upon irradiation, the photosensitizer situated in a specific tumor tissue is activated from the ground singlet state to the first excited state and next, by the chain of transitions, to the triplet state.…”
The study’s aim was to synthesize new unsymmetrical sulfanyl zinc(II) porphyrazines and subject them to physicochemical and electrochemical characterization and also an initial acute toxicity assessment. The procedure was initiated from a commercially available dimercaptomaleonitrile disodium salt and o-phthalonitrile using Linstead’s macrocyclization reaction conditions, which led to magnesium(II) tribenzoporphyrazine with 4-(3,5-dibutoxycarbonylphenoxy)butylthio substituents. The obtained macrocycle was demetallated with trifluoroacetic acid and subsequently remetallated with zinc(II) acetate toward the zinc(II) porphyrazine derivative. The zinc(II) tribenzoporphyrazine with 4-(3,5-dibutoxycarbonylphenoxy)butylthio substituents was then subjected to the reduction reaction with LiAlH4, yielding zinc(II) tribenzoporphyrazine with 4-[3,5-di(hydroxymethyl)phenoxy]butylthio substituents. The new zinc(II) tribenzoporphyrazines were characterized by UV-Vis spectroscopy, various NMR techniques (1HNMR, 13CNMR, 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC), and mass spectrometry. In the UV-Vis spectra, both macrocycles revealed characteristic Soret and Q-bands, whose positions were dependent on the solvent used for the measurements. Zinc(II) tribenzoporphyrazines were studied using electrochemical and photochemical methods, including the singlet oxygen generation assessment. Both zinc(II) porphyrazines revealed high singlet oxygen generation quantum yield values of up to 0.59 in DMSO, which indicates their potential photosensitizing potential for photodynamic therapy. In addition, new derivatives were subjected to a Microtox® bioluminescence assay.
“…It was found by Gierszewski et al [38] that porphyrazines with eight peripheral isophtaloxyalkylsulfanyl substituents generate singlet oxygen with Φ ∆ values between 0.01 and 0.04 in DMF and that incorporating Mg 2+ ions into the Pzs improves their capability to generate single oxygen. The exchange of Mg 2+ (3,6) to Zn 2 (4, 7) in the tribenzoporphyrazine ring influenced the singlet oxygen generation quantum yield values, which increased from 0.05 (3) to 0.24 (4) and from 0.20 (6) to 0.59 (7). In Figures 7 and 8, the Q-bands of 6 and 7 demonstrate only minimal to no changes during irradiation, thus indicating their good stability during measurements.…”
Section: Singlet Oxygen Generation Studymentioning
confidence: 95%
“…Metal-free Pz derivative 5 (92 mg, 0.075 mmol), N,N-dimethylformamide (DMF, 25 mL), and zinc(II) acetate (41 mg, 0.225 mmol) were stirred in a round-bottomed flask under inert gas at 70 • C for 24 h. After that, the solvent was evaporated, and the residual blue oil was subjected to column chromatography (dichloromethane/methanol 50:1 then 20:1), leading to a cerulean blue product 6 (79 mg, 71% yield). R f = 0.71 (dichloromethane/methanol, 20:1, v/v (7) Lithium aluminum hydride (13 mg, 0.353 mmol) was suspended in tetrahydrofuran (THF) precooled to 0 • C and stirred for 30 min. Porphyrazine derivative 6 (95 mg, 0.074 mmol) was dissolved in THF (14 mL), and the solution was added dropwise to the reaction mixture over 40 min.…”
Section: Synthetic Proceduresmentioning
confidence: 99%
“…The absorption of light in the range of 650-850 nm, which is often described as the phototherapeutic window, as well as the generation of reactive oxygen species in the photodynamic reaction, make Pzs especially relevant for medical applications, in particular photodynamic therapy (PDT) [6]. The PDT principle is based on the photodynamic reaction, which starts from the exposure of the photosensitizer to light of an appropriate wavelength [7]. Upon irradiation, the photosensitizer situated in a specific tumor tissue is activated from the ground singlet state to the first excited state and next, by the chain of transitions, to the triplet state.…”
The study’s aim was to synthesize new unsymmetrical sulfanyl zinc(II) porphyrazines and subject them to physicochemical and electrochemical characterization and also an initial acute toxicity assessment. The procedure was initiated from a commercially available dimercaptomaleonitrile disodium salt and o-phthalonitrile using Linstead’s macrocyclization reaction conditions, which led to magnesium(II) tribenzoporphyrazine with 4-(3,5-dibutoxycarbonylphenoxy)butylthio substituents. The obtained macrocycle was demetallated with trifluoroacetic acid and subsequently remetallated with zinc(II) acetate toward the zinc(II) porphyrazine derivative. The zinc(II) tribenzoporphyrazine with 4-(3,5-dibutoxycarbonylphenoxy)butylthio substituents was then subjected to the reduction reaction with LiAlH4, yielding zinc(II) tribenzoporphyrazine with 4-[3,5-di(hydroxymethyl)phenoxy]butylthio substituents. The new zinc(II) tribenzoporphyrazines were characterized by UV-Vis spectroscopy, various NMR techniques (1HNMR, 13CNMR, 1H-1H COSY, 1H-13C HSQC, and 1H-13C HMBC), and mass spectrometry. In the UV-Vis spectra, both macrocycles revealed characteristic Soret and Q-bands, whose positions were dependent on the solvent used for the measurements. Zinc(II) tribenzoporphyrazines were studied using electrochemical and photochemical methods, including the singlet oxygen generation assessment. Both zinc(II) porphyrazines revealed high singlet oxygen generation quantum yield values of up to 0.59 in DMSO, which indicates their potential photosensitizing potential for photodynamic therapy. In addition, new derivatives were subjected to a Microtox® bioluminescence assay.
“…Has been carried out by combining second-generation photosensitizers with receptor molecules to the desired target, such as proteins or lipoproteins that are used by pathogenic cells for their proliferation, monoclonal antibodies targeting a specific antigen of the target cell, surface markers such as, growth factors, hormones, or transferrin receptors ( Muehlmann et al, 2014 ; Zhang et al, 2018 ). These strategies allow greater delivery of the photosensitizer to the target tissue, that is, greater selectivity, which improves the effectiveness of PDT, in addition to decreasing the doses needed for desired therapeutic responses ( Calixto et al, 2016 ; Zhou et al, 2021 ).…”
Tissue engineering (TE) connects principles of life sciences and engineering to develop biomaterials as alternatives to biological systems and substitutes that can improve and restore tissue function. The principle of TE is the incorporation of cells through a 3D matrix support (scaffold) or using scaffold-free organoid cultures to reproduce the 3D structure. In addition, 3D models developed can be used for different purposes, from studies mimicking healthy tissues and organs as well as to simulate and study different pathologies. Photodynamic therapy (PDT) is a non-invasive therapeutic modality when compared to conventional therapies. Therefore, PDT has great acceptance among patients and proves to be quite efficient due to its selectivity, versatility and therapeutic simplicity. The PDT mechanism consists of the use of three components: a molecule with higher molar extinction coefficient at UV-visible spectra denominated photosensitizer (PS), a monochromatic light source (LASER or LED) and molecular oxygen present in the microenvironment. The association of these components leads to a series of photoreactions and production of ultra-reactive singlet oxygen and reactive oxygen species (ROS). These species in contact with the pathogenic cell, leads to its target death based on necrotic and apoptosis ways. The initial objective of PDT is the production of high concentrations of ROS in order to provoke cellular damage by necrosis or apoptosis. However, recent studies have shown that by decreasing the energy density and consequently reducing the production of ROS, it enabled a specific cell response to photostimulation, tissues and/or organs. Thus, in the present review we highlight the main 3D models involved in TE and PS most used in PDT, as well as the applications, future perspectives and limitations that accompany the techniques aimed at clinical use.
“…Still, some studies have also demonstrated that inorganic PS can be targeted to specific tissues, which represents a great advantage in its use for photodynamic therapy. 12 …”
Low oxygen concentration
inside the tumor microenvironment represents
a major barrier for photodynamic therapy of many malignant tumors,
especially urothelial bladder cancer. In this context, titanium dioxide,
which has a low cost and can generate high ROS levels regardless of
local O
2
concentrations, could be a potential type of photosensitizer
for treating this type of cancer. However, the use of UV can be a
major disadvantage, since it promotes breakage of the chemical bonds
of the DNA molecule on normal tissues. In the present study, we focused
on the cytotoxic activities of a new material (Ti(OH)
4
)
capable of absorbing visible light and producing high amounts of ROS.
We used the malignant bladder cell line MB49 to evaluate the effects
of multiple concentrations of Ti(OH)
4
on the cytotoxicity,
proliferation, migration, and production of ROS. In addition, the
mechanisms of cell death were investigated using FACS, accumulation
of lysosomal acid vacuoles, caspase-3 activity, and mitochondrial
electrical potential assays. The results showed that exposure of Ti(OH)
4
to visible light stimulates the production of ROS and causes
dose-dependent necrosis in tumor cells. Also, Ti(OH)
4
was
capable of inhibiting the proliferation and migration of MB49 in low
concentrations. An increase in the mitochondrial membrane potential
associated with the accumulation of acid lysosomes and low caspase-3
activity suggests that type II cell death could be initiated by autophagic
dysfunction mechanisms associated with high ROS production. In conclusion,
the characteristics of Ti(OH)
4
make it a potential photosensitizer
against bladder cancer.
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