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Photodiagnosis and Photodynamic Therapy Dec 2023Aminolevulinic acid-photodynamic therapy (ALA-PDT) is gaining attention as a potential method for treating select cancers due to its high specificity and low side effect...
BACKGROUND
Aminolevulinic acid-photodynamic therapy (ALA-PDT) is gaining attention as a potential method for treating select cancers due to its high specificity and low side effect feature. ALA enters cancer cells and accumulate as protoporphyrin IX (PpIX), which will then trigger phototoxicity following light irradiation. However, it is reported that some cancer cells have reduced efficacy of ALA-PDT due to high expression of ABCG2, a transporter involved in the PpIX efflux. In this study, we evaluated the effect of mangostin, a natural compound containing anti-tumor property, on the efficacy of ALA-PDT against cancer and the mechanism involved.
METHODS
We utilized TMK1 gastric cancer cell line, which has high ABCG2 expression, to evaluate the PpIX accumulation and phototoxicity exerted by ALA and mangostin co-addition.
RESULTS
We found that co-addition of ALA and mangostin significantly increase the phototoxicity and PpIX accumulation in TMK1 cells. We also investigated the effect of mangostin on porphyrin-heme pathway enzymes and ABCG2 and found that the addition of mangostin reduce the activity of ABCG2, reducing PpIX efflux.
CONCLUSION
These findings suggest that mangostin enhances the efficacy of ALA-PDT in cancer through inhibition of ABCG2 activity.
Topics: Aminolevulinic Acid; Photochemotherapy; Photosensitizing Agents; Cell Line, Tumor; Protoporphyrins; Neoplasms; Xanthones
PubMed: 37696317
DOI: 10.1016/j.pdpdt.2023.103798 -
Environment International Feb 2024Nowadays artificial light highly increases human exposure to light leading to circadian rhythm and sleep perturbations. Moreover, excessive exposure of ocular structures...
BACKGROUND
Nowadays artificial light highly increases human exposure to light leading to circadian rhythm and sleep perturbations. Moreover, excessive exposure of ocular structures to photons can induce irreversible retinal damage. Meta-analyses showed that sunlight exposure influences the age of onset and the progression of Age-related macular degeneration (AMD), the leading cause of blindness in people over fifty-year old. Currently, the blue-light hazard (BLH) curve is used in the evaluation of the phototoxicity of a light source for domestic lighting regulations.
OBJECTIVES
Here, we analyze the phototoxicity threshold in rats and investigate the role played by the light spectrum, assessing the relevance of the use of the BLH-weighting to define phototoxicity.
METHODS
We exposed albino rats to increasing doses of blue and white light, or to lights of different colors to evaluate the impact of each component of the white light spectrum on phototoxicity. Cellular mechanisms of cell death and cellular stress induced by light were analyzed.
RESULTS
Our results show that the phototoxicity threshold currently accepted for rats is overestimated by a factor of 50 when considering blue light and by a factor of 550 concerning white light. This is the result of the toxicity induced by green light that increases white light toxicity by promoting an inflammatory response. The content of green in white light induces 8 fold more invasion of macrophages in the retina than the content of blue light. Moreover, the use of BLH-weighting does not evaluate the amount of red radiations contained in white light that mitigates damage by inhibiting the nuclear translocation of L-DNase II and reducing by 33% the number of TUNEL-positive cells.
DISCUSSION
These findings question the current methods to determine the phototoxicity of a light source and show the necessity to take into account the entire emission spectrum. As current human phototoxicity thresholds were estimated with the same methods used for rats, our results suggest that they might need to be reconsidered.
Topics: Animals; Rats; Blue Light; Lighting; Retina
PubMed: 38335626
DOI: 10.1016/j.envint.2024.108471 -
Chemical Research in Toxicology Jul 2023Unraveling the causes underlying polycyclic aromatic hydrocarbon phototoxicity is an essential step in understanding the harmful effects of these compounds in nature....
Unraveling the causes underlying polycyclic aromatic hydrocarbon phototoxicity is an essential step in understanding the harmful effects of these compounds in nature. Toward this end, we have studied the DNA interactions and photochemistry of -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride in the presence and absence of NaF, KF, NaCl, KCl, NaBr, KBr, NaI, and KI (350 nm hν, pH 7.0). Exposing pUC19 plasmid to UV light in solutions containing 400 mM KCl formed significantly more direct strand breaks in DNA compared to no-salt control reactions. In contrast, NaCl increased DNA damage moderately, while the sodium(I) and potassium(I) fluoride, bromide, and iodide salts generally inhibited cleavage (I > Br > F). A halide anion-induced heavy-atom effect was indicated by monitoring anthracene photodegradation and by employing the hydroxyl radical (OH) probe hydroxyphenyl fluorescein (HPF). These studies revealed that among no-salt controls and the eight halide salts, only NaCl and KCl enabled the anthracene to photosensitize the production of high levels of DNA-damaging reactive oxygen species (ROS). Pre-irradiation of -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride at 350 nm increased the amounts of chloride salt-induced OH detected by HPF in subsequent anthracene photoactivation experiments. Taking into consideration that OH and other highly reactive ROS are extremely short-lived, this result suggests that the pre-irradiation step might lead to the formation of oxidized anthracene photoproducts that are exceedingly redox-active. The fluorometric probes HPF and Singlet Oxygen Sensor Green revealed that KCl concentrations ranging from 150 to 400 mM and from 100 to 400 mM, respectively, enhanced -(anthracen-9-ylmethyl)ethane-1,2-diaminium dichloride photosensitized OH and singlet oxygen (O) production over no-salt controls. Considering the relatively high levels of Na, K, and Cl ions that exist in the environment and in living organisms, our findings may be relevant to the phototoxic effects exhibited by anthracenes and other polycyclic hydrocarbons .
Topics: Humans; Chlorides; Sodium Chloride; Singlet Oxygen; Reactive Oxygen Species; Salts; Dermatitis, Phototoxic; Anthracenes; DNA
PubMed: 37347986
DOI: 10.1021/acs.chemrestox.2c00235 -
Biomedicine & Pharmacotherapy =... Nov 2023Talazoparib (TLZ) is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor employed for the treatment of breast cancer. This drug displays an absorption band...
Talazoparib (TLZ) is a poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitor employed for the treatment of breast cancer. This drug displays an absorption band in the UVA region, and therefore investigation of the possible phototoxic side-effects associated to its administration results of enormous relevance. In this context, we describe here a photochemical and photobiological study to ascertain the photosafety profile of TLZ. Concerning transient species, the singlet and triplet excited states of TLZ were detected by fluorescence (λ = 440 nm) and laser flash photolysis experiments (λ = 400 nm), respectively. Remarkably, TLZ irradiation with UVA light in aqueous solution resulted in formation of a stable photooxidated product, TLZ-P, whose absorption band is extended until the visible region. From in vitro experiments, phototoxicity was revealed for the parent drug by neutral red uptake (NRU) assays, with a PIF value of ca 7; besides, TLZ induced formation of reactive oxygen species (ROS) and produced significant damage to both proteins and DNA. By contrast, the singlet and triplet excited states of TLZ-P were not detected, and no photodamage was observed in the NRU experiments. Overall, the results indicate that TLZ induces phototoxicity, whereas its photoproduct exhibits photosafety.
Topics: Humans; Poly(ADP-ribose) Polymerase Inhibitors; Dermatitis, Phototoxic; Light; Reactive Oxygen Species; Photosensitizing Agents; Pharmaceutical Preparations
PubMed: 37793275
DOI: 10.1016/j.biopha.2023.115593 -
Journal of Biomedical Optics Mar 2024Label-free nonlinear optical microscopy has become a powerful tool for biomedical research. However, the possible photodamage risk hinders further clinical applications.
SIGNIFICANCE
Label-free nonlinear optical microscopy has become a powerful tool for biomedical research. However, the possible photodamage risk hinders further clinical applications.
AIM
To reduce these adverse effects, we constructed a new platform of simultaneous label-free autofluorescence multi-harmonic (SLAM) microscopy, featuring four-channel multimodal imaging, inline photodamage monitoring, and pulse repetition-rate tuning.
APPROACH
Using a large-core birefringent photonic crystal fiber for spectral broadening and a prism compressor for pulse pre-chirping, this system allows users to independently adjust pulse width, repetition rate, and energy, which is useful for optimizing imaging conditions towards no/minimal photodamage.
RESULTS
It demonstrates label-free multichannel imaging at one excitation pulse per image pixel and thus paves the way for improving the imaging speed by a faster optical scanner with a low risk of nonlinear photodamage. Moreover, the system grants users the flexibility to autonomously fine-tune repetition rate, pulse width, and average power, free from interference, ensuring the discovery of optimal imaging conditions with high SNR and minimal phototoxicity across various applications.
CONCLUSIONS
The combination of a stable laser source, independently tunable ultrashort pulse, photodamage monitoring features, and a compact design makes this new system a robust, powerful, and user-friendly imaging platform.
Topics: Lasers; Photons; Nonlinear Optical Microscopy; Microscopy, Fluorescence, Multiphoton
PubMed: 38487259
DOI: 10.1117/1.JBO.29.3.036501 -
Molecules (Basel, Switzerland) Aug 2023Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of...
Thienopyrimidines are structural analogs of quinazolines, and the creation of new 2-alkyl derivatives of ethyl 4-aminothienopyrimidine-6-carboxylates for the study of their anti-proliferative properties is of great pharmacological interest. Some 2-alkyl-4-amino-thieno[2,3-]pyrimidines - were synthesized, and their cyto- and phototoxicity against BALB 3T3 cells were established by an in vitro 3T3 NRU test. The obtained results indicate that the tested compounds are not cytotoxic or phototoxic, and that they are appropriate to be studied for their anti-proliferative and anti-tumor properties. The anti-proliferative potential of the compounds was investigated on MCF-7 and MDA-MB-231 cancer cells, as well as a MCF-10A cell line (normal human mammary epithelial cells). The most toxic to MCF-7 was thienopyrimidine with IC 13.42 μg/mL (IC 0.045 μM), followed by compound (IC 28.89 μg/mL or IC 0.11 μM). The thienopyrimidine revealed higher selectivity to MCF-7 and lower activity (IC 367 μg/mL i.e., 1.4 μM) than compound with MCF-10A cells. With respect to MDA-MB-231 cells, ester manifested the highest effect with IC 52.56 μg/mL (IC 0.16 μM), and 2-ethyl derivative revealed IC 62.86 μg/mL (IC 0.24 μM). It was estimated that the effect of the substances on the cell cycle progression was due to cell cycle arrest in the G2 stage for MDA-MB-231, while arrest in G1 was detected for the estrogen (ER)-positive MCF-7 cell line. The tested compound's effects on the change of the zeta potential in the tumorigenic cells utilized in this study were determined. The calculation which we performed of the physicochemical properties and pharmacokinetic parameters influencing the biological activity suggested high intestinal absorption, as well as drug-likeness.
Topics: Animals; Mice; Humans; Estrogens; BALB 3T3 Cells; Carboxylic Acids; Carcinogenesis; Dermatitis, Phototoxic; MCF-7 Cells
PubMed: 37687177
DOI: 10.3390/molecules28176347 -
Molecules (Basel, Switzerland) Nov 2023The aim of this study is to prepare redox-sensitive nanophotosensitizers for the targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was...
The aim of this study is to prepare redox-sensitive nanophotosensitizers for the targeted delivery of chlorin e6 (Ce6) against cervical cancer. For this purpose, Ce6 was conjugated with β-cyclodextrin (bCD) via a disulfide bond, creating nanophotosensitizers that were fabricated for the redox-sensitive delivery of Ce6 against cancer cells. bCD was treated with succinic anhydride to synthesize succinylated bCD (bCDsu). After that, cystamine was attached to the carboxylic end of bCDsu (bCDsu-ss), and the amine end group of bCDsu-ss was conjugated with Ce6 (bCDsu-ss-Ce6). The chemical composition of bCDsu-ss-Ce6 was confirmed with H and C NMR spectra. bCDsu-ss-Ce6 nanophotosensitizers were fabricated by a dialysis procedure. They formed small particles with an average particle size of 152.0 ± 23.2 nm. The Ce6 release rate from the bCDsu-ss-Ce6 nanophotosensitizers was accelerated by the addition of glutathione (GSH), indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive photosensitizer delivery capacity. The bCDsu-ss-Ce6 nanophotosensitizers have a low intrinsic cytotoxicity against CCD986Sk human skin fibroblast cells as well as Ce6 alone. However, the bCDsu-ss-Ce6 nanophotosensitizers showed an improved Ce6 uptake ratio, higher reactive oxygen species (ROS) production, and phototoxicity compared to those of Ce6 alone. GSH addition resulted in a higher Ce6 uptake ratio, ROS generation, and phototoxicity than Ce6 alone, indicating that the bCDsu-ss-Ce6 nanophotosensitizers have a redox-sensitive biological activity in vitro against HeLa human cervical cancer cells. In a tumor xenograft model using HeLa cells, the bCDsu-ss-Ce6 nanophotosensitizers efficiently accumulated in the tumor rather than in normal organs. In other words, the fluorescence intensity in tumor tissues was significantly higher than that of other organs, while Ce6 alone did not specifically target tumor tissue. These results indicated a higher anticancer activity of bCDsu-ss-Ce6 nanophotosensitizers, as demonstrated by their efficient inhibition of the growth of tumors in an in vivo animal tumor xenograft study.
Topics: Animals; Female; Humans; Photochemotherapy; HeLa Cells; Reactive Oxygen Species; Cell Line, Tumor; Uterine Cervical Neoplasms; Photosensitizing Agents; Chlorophyllides; beta-Cyclodextrins; Oxidation-Reduction; Porphyrins; Nanoparticles
PubMed: 37959817
DOI: 10.3390/molecules28217398 -
Bioresource Technology Oct 2023Microalgae, originating from a tertiary treatment of municipal wastewater, is considered a sustainable feedstock for producing biochar and hydrochar, offering great...
Microalgae, originating from a tertiary treatment of municipal wastewater, is considered a sustainable feedstock for producing biochar and hydrochar, offering great potential for agricultural use due to nutrient content and carbon storage ability. However, there are risks related to contamination and these need to be carefully assessed to ensure safe use of material from wastewater microalgae. Therefore, this study compared the properties and phototoxicity of biochar and hydrochar produced via pyrolysis and hydrothermal carbonisation (HTC) of microalgae under different temperatures and residence times. While biochar promoted germination and seedling growth by up to 11.0% and 70.0%, respectively, raw hydrochar showed strong phytotoxicity, due to the high content of volatile matter. Two post-treatments, dichloromethane (DCM) washing and further pyrolysis, proved to be effective methods for mitigating phytotoxicity of hydrochar. Additionally, biochar had 35.8-38.6% fixed carbon, resulting in higher carbon sequestration potential compared to hydrochar.
Topics: Wastewater; Microalgae; Biomass; Temperature; Carbon
PubMed: 37506941
DOI: 10.1016/j.biortech.2023.129567 -
Nucleic Acids Research Jul 2023Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this...
Photodynamic therapy (PDT) ideally relies on the administration, selective accumulation and photoactivation of a photosensitizer (PS) into diseased tissues. In this context, we report a new heavy-atom-free fluorescent G-quadruplex (G4) DNA-binding PS, named DBI. We reveal by fluorescence microscopy that DBI preferentially localizes in intraluminal vesicles (ILVs), precursors of exosomes, which are key components of cancer cell proliferation. Moreover, purified exosomal DNA was recognized by a G4-specific antibody, thus highlighting the presence of such G4-forming sequences in the vesicles. Despite the absence of fluorescence signal from DBI in nuclei, light-irradiated DBI-treated cells generated reactive oxygen species (ROS), triggering a 3-fold increase of nuclear G4 foci, slowing fork progression and elevated levels of both DNA base damage, 8-oxoguanine, and double-stranded DNA breaks. Consequently, DBI was found to exert significant phototoxic effects (at nanomolar scale) toward cancer cell lines and tumor organoids. Furthermore, in vivo testing reveals that photoactivation of DBI induces not only G4 formation and DNA damage but also apoptosis in zebrafish, specifically in the area where DBI had accumulated. Collectively, this approach shows significant promise for image-guided PDT.
Topics: Animals; DNA; DNA Damage; DNA Replication; G-Quadruplexes; Genomic Instability; Neoplasms; Oxidative Stress; Photosensitizing Agents; Zebrafish; Photochemotherapy
PubMed: 37191066
DOI: 10.1093/nar/gkad365 -
Pharmaceutics Aug 2023Photodynamic therapy (PDT) is a great potential anti-tumor therapy owing to its non-invasiveness and high spatiotemporal selectivity. However, systemically administered...
Photodynamic therapy (PDT) is a great potential anti-tumor therapy owing to its non-invasiveness and high spatiotemporal selectivity. However, systemically administered photosensitizers diffuse in the skin and the eyes for a long duration, which cause phototoxicity to bright light and sunlight. Therefore, following PDT, patients must avoid exposure of to light and sunlight to avoid this phototoxicity. In this study, we have developed a locally administered PDT using nano-adhesive porphyrin with polycations consisting of quaternary ammonium salt groups (aHP) as a photosensitizer. The aHP, approximately 3.0 nm in diameter, adhered the negatively charged cell membrane via electrostatic interaction. The aHP localized to the endosome via cell adhesion and induced apoptosis upon 635 nm light irradiation. On being administered subcutaneously on the tumor, 30% of the injected aHP remained in the administered sites. However, low-molecular-weight hematoporphyrin dihydrochloride (HP) disappeared due to rapid diffusion. PDT with locally administered aHP showed a higher anti-tumor effect after light irradiation at 635 nm for three days compared to low-molecular-weight HP. Intraperitoneal administration of HP caused severe phototoxicity upon irradiation with ultraviolet A at 10 J cm, whereas aHP did not cause phototoxicity because its diffusion into the skin could be suppressed, probably due to the high-molecular weight of aHP. Therefore, locally administered PDT with aHP is a potential PDT having high therapeutic efficacy without phototoxicity.
PubMed: 37631290
DOI: 10.3390/pharmaceutics15082076