Photochemistry and Photobiology最新文献

Skin photosensitization is a common challenge following intravenous administration of many photodynamic therapy (PDT) drugs, typically lasting days, weeks, or months in laboratory animals and patients. Symptoms of photosensitivity manifest as erythema and edema on skin exposed to sunlight or bright artificial lighting. Recent efforts using nanocarriers to increase photosensitizer accumulation in tumors have also been shown to reduce skin photosensitivity. We previously developed phototheranostic PORPHYSOME (PS) nanoparticles self-assembled from porphyrin-lipid conjugates and capable of potent anti-tumor PDT. Here, we demonstrate in a nonpigmented rat skin model that PS exhibit less severe and shorter-lasting skin photosensitivity compared with an equivalent drug dose of porfimer sodium (PHO), the canonical first-generation PDT drug. At 2, 4, 8, and 12 days post intravenous injection, depilated skin was exposed to escalating doses of simulated solar light. Light exposure 4 days post-injection showed markedly reduced symptoms of skin photosensitivity with PS than PHO. By Day 8, the minimal dose of light eliciting any kind of skin reaction was significantly higher with PS than PHO, and by Day 12, there was no detectable skin response with PS. These differences were attributed to altered intradermal distribution and faster clearance of PS vs. PHO in rat skin.

Despite evidence that visible light (VL) has similar effects on human skin as those of UVA, VL is often viewed as harmless. High SPF sunscreen prevents erythema but can lead to overexposure to UVA and VL, with unknown consequences. To explore the impact of chronic blue light exposure, we irradiated (50 J/cm², λ = 408 nm, three times a week) human immortalized keratinocytes under acute (3 irradiations), intermediate (14 irradiations), and chronic (42 irradiations) blue light exposure, monitoring phenotypic and gene expression changes. Chronically exposed keratinocytes exhibit increased nuclei area, chromatin alterations, higher proliferation, and apoptosis resistance, mirroring the consequences of chronic UVA exposure. While acute exposure upregulated keratinization and downregulated tissue repair and apoptosis genes, chronically exposed cells had upregulated genes involved in energy metabolism and oxidative phosphorylation, and downregulated genes were enriched for immune and inflammatory responses. Specific transcription factors were identified in both the acute and chronic stages, some of which have been associated with UVB exposure. IRF1, EGR1, ELF3, FOSL1, and CENPX, SRF, CEBPB, KLF4 were identified in the acute and chronic stages, respectively. We identified some changes in chronically irradiated keratinocytes similar to malignant transformation, emphasizing the need for further research on the long-term impacts of blue light exposure on human skin.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer due to a lack of targetable receptors and a high rate of metastasis. The current standard of care for TNBC involves neoadjuvant chemotherapy, such as doxorubicin (DOX), a systemic intervention that affects both cancerous and healthy growing cells throughout the body. In contrast, photodynamic therapy (PDT) offers a minimally invasive alternative, utilizing photosensitizers like benzoporphyrin derivative (BPD) activated by a specific wavelength of light to induce localized cell death. While PDT, both as a standalone treatment and in combination with chemotherapy, has been shown to enhance treatment efficacy in TNBC, its effects on metastatic potential remain poorly understood. To address this knowledge gap, we utilize in vitro assays characterizing cell morphology and invasion as predictors of in vivo metastasis of human TNBC cell lines (BT-20, MDA-MB-231, LM2) following treatments with BPD-PDT alone and in combination with DOX. In this study, we observed that both treatments administered individually demonstrated high sensitivity in BT-20 cells, moderate sensitivity in LM2 cells, and the lowest sensitivity in MDA-MB-231 cells. Comparatively, we found that the combination treatment is most synergistic in LM2 cells and least in BT-20 cells. To assess metastatic potential, we characterized changes in in vitro cell morphology after administering BPD-PDT alone. We discovered that sublethal doses of BPD-PDT alone reduce 3D single-cell and spheroid invasion in LM2 and BT-20 cells, suggesting a decrease in metastatic potential. In contrast, the combination treatment reduced spheroid invasion and led to a more significant increase in pro-apoptotic factors in LM2 and MDA-MB-231 cells compared to BT-20 cells. Overall, our findings highlight the distinct impacts of BPD-PDT alone and the synergistic effects of combination treatment on metastatic potential in TNBC.

Glioblastoma multiforme (GBM) is the most aggressive primary brain tumor, with a median overall survival of 14.6 months. GBM is incurable because of its invasive growth. These local invasive cells, most significantly glioblastoma stem cells (GSCs), when left behind, resist standard treatment, and cause almost all recurrences. However, the treatment of these infiltrative margins remains a significant challenge, as there are currently no options to reach these margins safely. Photodynamic therapy (PDT) shows promise as localized treatment option using light-activated compounds that target tumor cells and that generate reactive oxygen species (ROS) to destroy them. Far red light, combined with silicon phthalocyanines, could penetrate deeper making it more effective for reaching cancer cells in the tumor margin without compromise of healthy brain. In this study, we used patient-derived GBM spheroids in vitro as a preclinical model to evaluate a new dual-cRGDfK-silicon phthalocyanine conjugate targeting integrin αvβ3, a protein expressed by GBM cells and vasculature. Targeted PDT was efficient in killing GSC spheroids, showing that the combination of far-red light with more precise targeting can reach the type of cells found in the invasive margin, using silicon phthalocyanine as the photosensitizer.

Despite advancements made in treatment options, cancer continues to be one of the leading causes of death worldwide. Photodynamic therapy (PDT) has gained attention as a minimally invasive and highly selective treatment option for cancer. However, challenges due to the hydrophobicity of photosensitizers and their poor tumor selectivity have limited their use in cancer therapy. Recent developments in nanotechnology, particularly the use of gold nanoparticles (AuNPs), help overcome these challenges. AuNPs provide a stable and biocompatible platform to deliver photosensitizers, improving their solubility, stability, and ability to target tumors while reducing side effects. Functionalized AuNPs take advantage of mechanisms like the enhanced permeability and retention (EPR) effect and active targeting, improving reactive oxygen species (ROS) production and overall therapeutic efficacy. This review explores innovations in AuNP-based PDT systems, including ligand-functionalized nanoparticles, bioresponsive coatings, and theranostic approaches that combine imaging with therapy. By delving into important aspects of synthesis, characterization, and functionalization, we show how AuNPs improve the delivery and performance of photosensitizers. For instance, systems functionalized with prostate-specific membrane antigen (PSMA) have shown increased therapeutic precision and efficacy in vivo. These advancements are paving the way for more targeted and safer cancer treatments, establishing AuNP-based PDT as a promising approach for developing highly effective oncological therapies with greater precision and fewer side effects.

In the United States, 8.2 million patients suffer from non-healing wounds which are often infected with antibiotic-resistant bacteria. Blue light (BL) and Sangre de Drago (Croton lechleri, SD) have potent mechanisms of antibacterial action through free radical formation and anti-biofilm effect, respectively. The aim of this pilot study was to evaluate the enhanced antibacterial effect of a novel combination treatment consisting of blue light and Sangre de Drago. Preliminary dosimetry measurements for effective SD concentration (5%) and 415-nm blue LED light fluence (125.3 J/cm² with a standard variation of 5 mW) were performed. E. coli K-12 (volume 0.1-mL, concentration 2 × 10⁵CFU/mL) was applied to each of 32 tryptic soy agar (TSA) plates. Inoculated TSA plates were separated into four groups: (1) no treatment (Control), (2) treatment with SD only, (3) treatment with blue light (BL) only, and (4) treatment with both SD and BL. Plates were incubated for 12 h at 37°C. Colony-forming units (CFUs) were analyzed using Image J software and count, size and overal TSA plate coverage were quantified. The median CFU count was highest in the Control group (157.9, interquartile range [IQR]: 112.0-157.9), followed by SD-only (60.5, IQR: 51.6-93.6), BL-only (33.7, IQR: 23.6-45.2), while no bacterial growth was observed in the combination treatment group (0, IQR: 0-0). The median CFU size was largest for control (0.44 mm², IQR: 0.35-0.59 mm²), followed by BL-only (0.28 mm², IQR: 0.19-0.43 mm²) and SD-only (0.16 mm², IQR: 0.11-0.23 mm²). BL-only caused a marked reduction in total CFU count, while the median CFU size was only moderately decreased compared to Control. The significant reduction in CFU count may be due to the bactericidal action of BL on bacteria. Conversely, SD-only caused just a moderate decrease in CFU count but had the largest decrease in median CFU size, indicating a possible strong bacteriostatic mechanism of action by SD. The combination of BL and SD resulted in no bacterial growth. The Bliss independence model demonstrated a Bliss synergy value of 0.04 indicating low synergy between the two treatments, even though its presence was significant (p = 0.001). This initial investigation on the combination treatment using 5% SD and 415-nm BL demonstrates synergy resulting in an enhanced antibacterial effect compared to each treatment alone. Further investigation and validation of these results is required. If validated, this novel combination approach may be translated to clinical practice to help treat chronic wounds infected with antimicrobial-resistant bacteria, using non-traditional antimicrobial agents that bypass the most common bacterial mechanisms of antibiotic resistance.

In recent years, there have been numerous reports on the synthesis and applications of 1,2,4,5-tetraphenylimidazole (TEPI) derivatives, particularly due to the photophysical properties of such systems. However, the long-lived emission behavior of TEPIs has not been studied, with research largely limited to attempts at 77 K. In this study, the compound 1-(4-chlorophenyl)-2,4,5-triphenyl-1H-imidazole (TEPI-Cl) was prepared and characterized using experimental techniques (i.e., absorption spectra, steady-state, and long-lived emission), as well as computationally, using a combination of Extended Tight Binding (xTB), Density Functional Theory (DFT), and Time-Dependent (TD-DFT) methods. TEPI-Cl exhibited a low solvatochromic effect, both in absorption and steady-state emission in organic solvents, which is typical of a locally excited transition; this was confirmed by the performed calculations. However, in its aggregated state (observed in water/acetonitrile mixtures with >80% of water, in volume), the compound displayed the emergence of a new band in the absorption spectrum, as well as aggregate-induced enhanced emission in the steady-state emission analysis. The long-lived emission spectrum of TEPI-Cl recorded at room temperature shows two signals (at 380 and 540 nm) and the presence of benzil enables the generation of triplet excited states of the latter, likely through an energy transfer process. The sensitivity of these signals to the presence of oxygen suggested that the related excited states are of a triplet nature; moreover, the calculated electronic transitions for the optimized structures of the T₁ and T₂ states are comparable to the experimentally observed long-lived emission wavelengths. This newly observed behavior of TEPI-Cl comes as a novel photophysical property added to this class of molecules, demonstrating its significant potential for further applications in complex matrices.

Plants may be a source of protective compounds that inhibit injuries caused by overexposure to solar radiation. Present work evaluated the protective effects of a phytochemical mixture based on Posoqueria latifolia extract + Kaempferol against ultraviolet-induced radiation DNA damage in human fibroblasts and mice skin. Cytotoxicity, genotoxicity, and antigenotoxicity of P. latifolia flower extract, Kaempferol, and the mixture of both were studied in MRC5 human fibroblasts using Trypan blue exclusion and Comet assays. Kinetics of DNA damage repair post irradiation, in the presence and absence of the phytochemicals, were also evaluated. The inhibition of UVB-induced erythema and cyclobutene pyrimidine dimers (CPD) by the phytochemicals and the mixture were also investigated in mice skin. We showed that the P. latifolia flower extract, Kaempferol, and the mixture inhibited UVB-induced DNA damage and increased DNA repair mechanisms in human fibroblasts. In addition, these phytochemicals inhibited the UVB-induced erythema and CPD in mice skin. The potential of the studied phytochemicals in human photoprotection was discussed.

Photodynamic therapy (PDT) is a minimally invasive treatment with low systemic toxicity and immunomodulatory effects, increasingly applied in managing HPV-associated cervical lesions. Toll-like receptors (TLRs) are critical in regulating immune responses in cervical pathology, yet their dynamics under PDT remain underexplored. This study investigates the effect of PDT on TLR2, TLR3, TLR4, and TLR8 expression in cervical epithelial cells ex vivo, considering lesion severity. The results reveal that TLR8 exhibited the most significant reduction across all groups 2 h after PDT, with the strongest suppression in patients with invasive cervical cancer. TLR4 expression decreased by 24% in HPV-infected patients and by 71% in those with cervical cancer, highlighting its potential role in modulating the inflammatory microenvironment post-PDT. TLR3 showed hyperexpression in LSIL and suppression in HSIL/CIN III, although changes were not statistically significant (p > 0.05). TLR2 expression remained unchanged, likely due to HPV type variability. These findings demonstrate that PDT effectively reduces hyperexpression of TLR8, TLR4, and TLR3 in early-stage cervical cancer, suggesting their potential as biomarkers for treatment efficacy. Further research incorporating HPV typing and advanced techniques like liquid biopsy is essential to refine our understanding of TLRs in PDT for HPV-associated cervical lesions.

Although age is not a contraindication for orthodontic treatment, it can be considered more challenging in mature adult patients, mainly due to a less responsive bone metabolism and reduced osteoblastic activity compared to young patients. In orthodontics, photobiomodulation (PBM) has shown positive results in bone remodeling during tooth movement. This study seeks to assess the effect of PBM can have a positive effect on bone remodeling, stimulating bone formation in middle-aged individuals and allowing for a better periodontal condition. Bone structure and the length of the roots were evaluated using cone beam computed tomography images before and after tooth movement and PBM in patients aged between 40 and 60 years. In addition, we aimed to evaluate the expression of the markers receptor activator of NFκB (RANK), osteoprotegerin (OPG), and osteopontin (OPN) presented in the crevicular fluid using the enzyme-linked immunosorbent assay test. Tooth movement was performed by intruding upper molars with two mini-implants as anchorage bilaterally. One side received PBM with light-emitting diode (LED) light and the contralateral side was used as control (no irradiation). The PBM equipment specially designed for this study consisted of six LEDs of 5 mW each, for 7 minutes, totaling 2 J, 3 times a week, for 5 months. The PMB group showed greater tooth movement (p < 0.05), an increase of 74% on average for bone height. PBM induced a significant increase in RANK expression at month 3 (p < 0.05), and the expression of OPG and OPN showed a significant increase in the fifth month of movement (p < 0.05) in the PBM group. PBM may represent an adjunct therapeutic approach during tooth movement in more mature patients, leading to a more responsive bone metabolism and favoring more comprehensive orthodontic treatment.