-
Photodiagnosis and Photodynamic Therapy Jun 2024Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid...
BACKGROUND
Photodynamic therapy (PDT) has been utilized as a promising alternative cancer treatment due to its minimum invasiveness over the years. Exogenous 5-aminolevulinic acid (ALA) triggers protoporphyrin IX (PpIX) accumulation, which happens in cancer cells. However, certain types of cancer exhibit reduced effectiveness in the PpIX accumulation mechanism. This study aimed to determine the effect of ALA-PDT combination with hemin on gastric carcinoma TMK-1 cells.
METHODS
This study utilized TMK-1 gastric cancer cell line to evaluate PpIX, ROS, and Fe accumulation following the administration of ALA, hemin, and a combination of ALA and hemin PDT. We also evaluate the mRNA expressions related to iron homeostasis and treatment impacts on cell viability.
RESULTS
The co-addition of ALA and hemin PDT for 4 h of treatment resulted in a significant decrease in cell viability by up to 18 %. While ALA-PDT enhanced PpIX metabolism, the addition of hemin influenced both the production of reactive oxygen species (ROS) and cellular iron homeostasis by inducing Fe accumulation and affecting mRNA levels of IRP, Tfr1, Ferritin, NFS1, and SDHB.
CONCLUSION
These findings suggest that the addition of ALA and hemin enhances phototoxicity in TMK-1 cells. The combination of ALA and hemin with PDT induces cell death, evidenced by increased cytotoxicity properties such as PpIX and ROS, along with significant changes in TMK-1 gastric cancer iron homeostasis. Therefore, the combination of ALA and hemin could be one of the alternatives in photodynamic therapy for cancer in the future.
PubMed: 38901716
DOI: 10.1016/j.pdpdt.2024.104253 -
Photochemistry and Photobiology Jun 2024Exposure to phototoxicants and photosensitizers can result in the generation of reactive oxygen species (ROS), leading to oxidative stress, DNA damage, and various...
Exposure to phototoxicants and photosensitizers can result in the generation of reactive oxygen species (ROS), leading to oxidative stress, DNA damage, and various skin-related issues such as aging, allergies, and cancer. While several photo-protectants offer defense against ultraviolet radiation (UV-R), their effectiveness is often limited by photo-instability. Sunset Yellow (SY), an FDA-approved food dye, possesses significant UV-R and visible light absorption properties. However, its photoprotective potential has remained unexplored. Our investigation reveals that SY exhibits remarkable photostability for up to 8 h under both UV-R and sunlight. Notably, SY demonstrates the ability to quench ROS, including singlet oxygen (O), superoxide radicals ( ), and hydroxyl radicals (·OH) induced by rose bengal, riboflavin and levofloxacin, respectively. Moreover, SY proves effective in protecting against the apoptotic and necrotic cell death induced by the phototoxicant chlorpromazine (CPZ) in HaCaT cells. Further, it was observed that SY imparts photoprotection by inhibiting intracellular ROS generation and calcium release. Genotoxicity evaluation provides additional evidence supporting SY's photoprotective effects against CPZ-induced DNA damage. In conclusion, these findings underscore the potential of SY as a promising photoprotective agent against the toxic hazards induced by phototoxicants, suggesting its prospective application in the formulation of broad-spectrum sunscreens.
PubMed: 38899585
DOI: 10.1111/php.13966 -
RSC Advances Jun 2024In recent years, photodynamic therapy (PDT) has garnered significant attention in cancer treatment due to its increased potency and non-invasiveness compared to...
In recent years, photodynamic therapy (PDT) has garnered significant attention in cancer treatment due to its increased potency and non-invasiveness compared to conventional therapies. Active-targeted delivery of photosensitizers (PSs) is a mainstay strategy to significantly reduce its off-target toxicity and enhance its phototoxic efficacy. The anti-melanoma inhibitory activity (MIA) antibody is a targeting biomolecule that can be integrated into a nanocarrier system to actively target melanoma cells due to its specific binding to MIA antigens that are highly expressed on the surface of melanoma cells. Gold nanoparticles (AuNPs) are excellent nanocarriers due to their ability to encapsulate a variety of therapeutics, such as PSs, and their ability to bind with targeting moieties for improved bioavailability in cancer cells. Hence, we designed a nanobioconjugate (NBC) composed of zinc phthalocyanine tetrasulfonic acid (ZnPcS), AuNPs and anti-MIA Ab to improve ZnPcS bioavailability and phototoxicity in two and three-dimensional tumour models. In summary, we demonstrated that this nanobioconjugate showed significant inhibitory effects on both melanoma models due to increased ROS yields and bioavailability of the melanoma cells compared to free ZnPcS
PubMed: 38895533
DOI: 10.1039/d4ra03858d -
Trends in Molecular Medicine Jun 2024Protoporphyrias are caused by pathogenic variants in genes encoding enzymes involved in heme biosynthesis. They induce the accumulation of a hydrophobic phototoxic... (Review)
Review
Protoporphyrias are caused by pathogenic variants in genes encoding enzymes involved in heme biosynthesis. They induce the accumulation of a hydrophobic phototoxic compound, protoporphyrin (PPIX), in red blood cells (RBCs). PPIX is responsible for painful cutaneous photosensitivity, which severely impairs quality of life. Hepatic elimination of PPIX increases the risk of cholestatic liver disease, requiring lifelong monitoring. Treatment options are scarce and mainly limited to supportive care such as protection from visible light. Here, we review the pathophysiology of protoporphyrias, their diagnosis, and current recommendations for medical care. We discuss new therapeutic strategies, some of which are currently undergoing clinical trials and are likely to radically alter the severity of the disease in the years to come.
PubMed: 38890030
DOI: 10.1016/j.molmed.2024.05.006 -
Analytical Chemistry Jun 2024Single-molecule localization microscopy (SMLM) requires high-intensity laser irradiation, typically exceeding kW/cm, to yield a sufficient photon count. However, this...
Single-molecule localization microscopy (SMLM) requires high-intensity laser irradiation, typically exceeding kW/cm, to yield a sufficient photon count. However, this intense visible light exposure incurs substantial cellular toxicity, hindering its use in living cells. Here, we developed a class of near-infrared (NIR) spontaneously blinking fluorophores for SMLM. These NIR fluorophores are a combination of rhodamine spirolactams and merocyanine derivatives, where the rhodamine spirolactam component converts between a bright and dark state based on pH-dependent spirocyclization and merocyanine derivatives shift the excitation wavelength into the infrared. Single-molecule characterizations demonstrated their potential for SMLM. At a moderate power density of 3.93 kW/cm, these probes exhibit duty cycle as low as 0.18% and an emission rate as high as 26,700 photons/s. Phototoxicity assessment under single-molecule imaging conditions reveals that NIR illumination (721 nm) minimizes harm to living cells. Employing these NIR fluorophores, we successfully captured time-lapse super-resolution tracking of mitochondria at a Fourier ring correlation (FRC) resolution of 69.4 nm and reconstructed the ultrastructures of endoplasmic reticulum (ER) in living cells.
PubMed: 38889184
DOI: 10.1021/acs.analchem.4c02445 -
Advanced Science (Weinheim,... Jun 2024Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors,...
Activatable type I photosensitizers are an effective way to overcome the insufficiency and imprecision of photodynamic therapy in the treatment of hypoxic tumors, however, the incompletely inhibited photoactivity of pro-photosensitizer and the limited oxidative phototoxicity of post-photosensitizer are major limitations. It is still a great challenge to address these issues using a single and facile design. Herein, a series of totally caged type I pro-photosensitizers (Pro-I-PSs) are rationally developed that are only activated in tumor hypoxic environment and combine two oxygen-independent therapeutic mechanisms under single-pulse laser irradiation to enhance the phototherapeutic efficacy. Specifically, five benzophenothiazine-based dyes modified with different nitroaromatic groups, BPN 1-5, are designed and explored as latent hypoxia-activatable Pro-I-PSs. By comparing their optical responses to nitroreductase (NTR), it is identified that the 2-methoxy-4-nitrophenyl decorated dye (BPN 2) is the optimal Pro-I-PSs, which can achieve NTR-activated background-free fluorescence/photoacoustic dual-modality tumor imaging. Furthermore, upon activation, BPN 2 can simultaneously produce an oxygen-independent photoacoustic cavitation effect and a photodynamic type I process at single-pulse laser irradiation. Detailed studies in vitro and in vivo indicated that BPN 2 can effectively induce cancer cell apoptosis through synergistic effects. This study provides promising potential for overcoming the pitfalls of hypoxic-tumor photodynamic therapy.
PubMed: 38885361
DOI: 10.1002/advs.202400462 -
Italian Journal of Dermatology and... Jun 2024Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin...
INTRODUCTION
Despite the promising results in terms of effectiveness of anticancer treatments, a wide range of dermatologic adverse reactions have been reported. Among them, skin photosensitivity, defined as a range of dermatologic conditions caused or exacerbated by sunlight exposure, is an emerging adverse event.
EVIDENCE ACQUISITION
A review of the current literature was performed to report the most characteristic phototoxic and photoallergic reactions associated with anticancer therapies, as well as other characteristic manifestations potentially related to photo-exposure, including UV recall, vitiligo-like reactions, drug-induced cutaneous lupus erythematosus, and UV-induced hyperpigmentation.
EVIDENCE SYNTHESIS
A total of 30 manuscripts were collected in the present review, reporting several phototoxic and photoallergic reactions associated with anticancer therapies.
CONCLUSIONS
Photosensitivity reactions are an increasing challenge in cancer management. The raising awareness about this adverse event has increased the identification of potential photosensitizing drugs as well as its prevention and the management. However, more studies are required to improve the knowledge of this cutaneous toxicity and to define a personalized treatment strategy.
PubMed: 38884533
DOI: 10.23736/S2784-8671.24.07782-X -
Bioorganic Chemistry Jun 2024Hyperpigmentation disorders may result from inappropriate melanin deposition and/or excessive melanin synthesis. They are classified mainly as aesthetic problems, but...
Hyperpigmentation disorders may result from inappropriate melanin deposition and/or excessive melanin synthesis. They are classified mainly as aesthetic problems, but they can significantly affect human health by decreasing self-esteem. There are available only limited treatment options for hyperpigmentation disorder, among others, cosmetic products applied topically. Depigmenting ingredients were found to be ineffective and characterized by various side effects. As a result, many efforts are made to discover novel, potent, and safe melanogenesis inhibitors for possible use in topical cosmetic depigmenting formulations. Cinnamic acid derivatives constitute a widely tested group for that purpose. This article reports research in the group of N-alkyl cinnamamide derivatives (un)substituted in phenyl ring. Among tested series, (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide (compound 21) showed the most promising inhibitory properties in mushroom tyrosinase assay (IC = 36.98 ± 1.07 µM for monophenolase activity, IC = 146.71 ± 16.82 µM for diphenolase activity) and melanin production inhibition in B16F10 mouse melanoma cell line at concentration 6.25 µM resulting probably from decreasing of Tyr, Mitf, Tyrp-1, and Tyrp-2 genes expression. This compound also showed melanin production inhibitory properties in pigmented reconstructed human epidermis when used in 1 % and 2 % solutions in 50 % PEG400. In vitro evaluation of its safety profile showed no cytotoxicity to human keratinocytes HaCaT, human skin fibroblasts BJ, and human primary epidermal melanocytes HEMa, no mutagenicity in the Ames test, no genotoxicity in micronucleus test, no phototoxicity, as well as no skin irritation potential tested in PEG400 solution. This compound was also shown to penetrate across the epidermis to reach the possible site of action. The performed research led to classify (E)-3-(4-chlorophenyl)-N-(5-hydroxypentyl)acrylamide as a novel potential depigmenting cosmetic ingredient.
PubMed: 38878750
DOI: 10.1016/j.bioorg.2024.107533 -
Frontiers in Oral Health 2024Chronic periodontitis is a ubiquitous inflammatory disease in dental healthcare that is challenging to treat due to its impact on bone and tooth loss. Conventional... (Review)
Review
Chronic periodontitis is a ubiquitous inflammatory disease in dental healthcare that is challenging to treat due to its impact on bone and tooth loss. Conventional mechanical debridement has been challenging in eliminating complex subgingival biofilms. Hence, adjunctive approaches like low-level laser antimicrobial photodynamic therapy (A-PDT) utilising methylene blue (MB) have been emerging approaches in recent times. This review evaluates the latest research on the use of MB-mediated A-PDT to decrease microbial count and enhance clinical results in chronic periodontitis. Studies have shown the interaction between laser light and MB generates a phototoxic effect thereby, eliminating pathogenic bacteria within periodontal pockets. Moreover, numerous clinical trials have shown that A-PDT using MB can reduce probing depths, improve clinical attachment levels, and decrease bleeding during probing in comparison to traditional treatment approaches. Notably, A-PDT shows superior antibiotic resistance compared to conventional antibiotic treatments. In conclusion, the A-PDT using MB shows promise as an adjunctive treatment for chronic periodontitis. Additional research is required to standardize treatment protocols and assess long-term outcomes of A-PDT with MB in the treatment of periodontitis.
PubMed: 38872983
DOI: 10.3389/froh.2024.1407201