Photochemistry and Photobiology最新文献

First-line treatment for advanced-stage or recurrent endometrial cancer consists of platinum- and taxane-based chemotherapy, to which many patients will develop resistance. Determining the factors that contribute to platinum resistance and developing alternate treatment options for patients with advanced-stage gynecologic malignancies is critical to improving survival outcomes. Recently, we published the first study evaluating the contribution of perfluoroalkyl substances (PFAS) exposure to platinum resistance in endometrial cancer cell lines and found that select PFAS induce carboplatin resistance, potentially by dysregulating mitochondrial function. The present study expands upon those findings by examining the efficacy of photodynamic priming (PDP) in combination with carboplatin to overcome PFAS-induced platinum resistance. Due to the suspected role of mitochondrial dysfunction in platinum resistance, two clinically approved photosensitizers that, in part, localize to mitochondrial membranes or are synthesized in mitochondria were evaluated: benzoporphyrin derivative (BPD) and aminolevulinic acid-induced protoporphyrin IX (ALA-PpIX), respectively. Combination of ALA-PpIX-mediated PDP + carboplatin resulted in a greater reduction in survival fraction than the same combination with BPD. While PDP with both photosensitizers reduced mitochondrial membrane potential, the reduction was greater with BPD-PDP than ALA-PpIX-PDP. These findings demonstrate that BPD-PDP and ALA-PpIX-PDP in combination with carboplatin can be used to overcome PFAS-induced platinum resistance in endometrial cancer cells.

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.

The ocular safety of 222-nm far-ultraviolet-C (UV-C) irradiation, widely recognized for its germicidal properties, was evaluated in a clinical setting to assess its long-term health effects on the human eye. This prospective observational study involved a 36-month follow-up of physicians working in an ophthalmic examination room equipped with 222-nm UV-C lamps. Initially, a 12-month observation showed no signs of acute or chronic ocular damage. To further substantiate these findings, the study period was extended to 36 months, during which four participants underwent regular ocular examinations, including assessments of visual acuity, refractive error, and corneal endothelial cell density. The irradiation dose was meticulously controlled to remain within the previous threshold limit of 22 mJ/cm² over an 8-h period, as advised by the ACGIH prior to 2022. Results indicated no significant changes in these parameters, suggesting no clinically significant ocular hazards associated with prolonged exposure to 222-nm UV-C irradiation under real-world conditions. Additionally, no delayed side effects, such as pterygium, keratopathies, or cataracts, were observed. Our study supports the safe use of 222-nm UV-C for microbial disinfection in occupied environments and provides a robust foundation for updated safety guidelines.

Photodynamic therapy (PDT) has shown promise as an adjuvant treatment for malignant pleural mesothelioma when combined with surgical resection. Accurate light dosimetry is critical for treatment efficacy. This study presents an improved method for analyzing light fluence distribution in pleural PDT using a standardized anatomical coordinate system and advanced computational modeling. We utilized an infrared navigation system with an improved treatment delivery wand to track light delivery in real-time. The human chest cavity geometry was reconstructed and the pleura was mapped to a standardized coordinate system, allowing for direct comparisons across patients. Light fluence was calculated using both primary and scattered components, with a novel dual correction method applied to match measured values at detector locations. The standardized approach allowed for statistical analysis of light fluence distribution across anatomical regions in a cohort of 11 patients. Results showed acceptable light fluence uniformity with a standard deviation of 6.6% from the prescribed dose across patients. This comprehensive analysis provides insights for optimizing treatment protocols and lays the groundwork for future studies on singlet oxygen generation and its correlation with treatment outcomes in pleural PDT.

Photodynamic therapy (PDT) is an attractive therapeutic and pest-controlling modality. This study aims to synthesize silver nanoparticles capped with copper chlorophyllin (AgNPs-CHL) and examine their anti-breast cancer, Musca domestica pesticide, and larvicidal activities. Silver nitrate was the precursor, and CHL was the capping agent. Nanoparticles were characterized using UV-VIS, TEM, XRD, and zeta sizer. The anticancer activity against MDA-MB-231 cells was examined by MTT assay, and flow cytometry was applied to study the mode of cell death. Nanoparticle cellular internalization was investigated by confocal laser scanning microscope. The same nanoparticles were fed to adult Musca domestica followed by sunlight exposure, and the lethality was quantified. Furthermore, the nanoparticles were fed to Musca domestica larvae followed by sunlight illumination, and the number of dead larvae was counted over 24 h. Results revealed success in synthesizing spherical AgNPs with an average diameter of 25 nm. AgNPs-CHL-induced apoptotic cell death in MDA-MB-231 and were sufficiently internalized within the cytoplasm. Sunlight exposure following 24 h of feeding resulted in 60% death of the adult Musca domestica and 75% death of the larvae. This is the first study to demonstrate the multi-activities of the synthesized AgNPs-CHL and encourages further studies.

Photodynamic therapy (PDT) is a targeted cancer treatment offering precise tumor ablation with minimal systemic toxicity. However, its clinical application is constrained by poor solubility, rapid clearance, and inadequate tumor accumulation of photosensitizers (PS). This study presents an innovative liquid metal nanoparticle (LMNP) platform, composed of gallium-indium eutectic alloy (EGaIn), engineered to address these drug delivery challenges in PDT. Using a one-step sonication process, EGaIn nanoparticles are synthesized and functionalized with folic acid (FA) for tumor-specific targeting, beta cyclodextrin (β-CD) for enhanced drug encapsulation, and benzoporphyrin derivative (BPD) as a PS. The inclusion of β-CD significantly improves the BPD loading capacity, achieving a three-fold enhancement (52% vs. 18%) while ensuring nanoparticle stability and sustained drug release. Covalent binding of FA and β-CD to the gallium oxide surface enables effective targeting and biocompatibility. In vitro analyses demonstrate potent PDT efficacy, even with reduced cellular uptake, underscoring the platform's ability to overcome intracellular delivery barriers. This LMNP-based nanoplatform addresses critical PDT limitations, such as suboptimal drug delivery and systemic toxicity, leveraging the unique chemical and physical properties of EGaIn nanoparticles. Its multifunctional design integrates targeted delivery, controlled release, and precise therapeutic activation, representing a promising advancement in the development of effective, personalized cancer treatment strategies.

Incomplete surgical resection in head and neck cancer can lead to locoregional recurrence in >35% of patients. Approaches such as image-guided surgery (IGS) and post-operative photodynamic therapy (PDT) have been proposed to reduce recurrence rates. However, the PDT doses needed to eliminate all unresected diseases are not established. This in vitro proof-of-concept study aims to predict head and neck tumor nodule viability in vitro following PDT with TLD1433 using the IGS probe ABY-029. ABY-029 is an EGFR-specific affibody-IRDye800CW conjugate that has undergone Phase 0 evaluation studies in head and neck cancer, among others. TLD1433 is a ruthenium-based photosensitizer in a Phase II trial for non-muscle invasive bladder cancer. Here, we demonstrate that decreases in fluorescence emission of ABY-029 bound to MOC1 mouse head and neck cancer nodules in vitro can be predictive of TLD1433 PDT responses. Results show that photoactivation of TLD1433 produces reactive oxygen species (ROS) that reduce MOC1 nodule fractional viability in a manner that is inversely correlated with ABY-029 fluorescence intensity (Pearson's r = -0.9148, R² = 0.8369, p < 0.0001). We hypothesize that this is due to ROS-mediated degradation of IRDye800CW. The findings warrant further studies using head and neck cancer nodules with heterogenous PDT responses and EGFR expression levels. If successful, the future goal would be to use ABY-029 to guide the dosimetry of intraoperative PDT of the surgical bed after IGS to eliminate all microscopic diseases, reduce recurrence rates, and prolong survival.

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.

Tumor-targeted, activatable photoimmunotherapy (taPIT) has shown promise in preclinical models to selectively eliminate drug-resistant micrometastases that evade standard treatments. Moreover, taPIT has the potential to resensitize chemo-resistant tumor cells to chemotherapy, making it a complementary modality for treating recurrent high-grade serous ovarian cancer (HGSOC). However, the established implementation of taPIT relies on the overexpression of EGFR in tumor cells, which is not universally observed in HGSOCs. Motivated by the need to expand taPIT applications beyond EGFR, we conducted mRNA-sequencing and proteomics to identify alternative cell surface targets for taPIT in patient-derived HGSOC cell cultures with weak EGFR expression and lacking expression of other cell surface proteins commonly reported in the literature as overexpressed in ovarian cancers, such as FOLR1 and EpCAM. Our findings highlight TFRC and LRP1 as promising alternative targets. Notably, TFRC was overexpressed in 100% (N = 5) of the patient-derived HGSOC models tested, whereas only 60% of models had high EpCAM expression, suggesting that future larger cohort studies should include TFRC. While this study focuses on target identification, future work will expand the approaches developed here to larger HGSOC biopsy repositories and will also develop and evaluate antibody-photosensitizer conjugates targeting these proteins for taPIT applications.

The objective of this study was to determine the effects of methylene blue (MB) concentration, laser fluence rate, and laser fluence on the efficacy of in vitro photodynamic therapy (PDT) for four bacteria commonly found in human abscesses. PDT experiments were performed with four of the most common bacteria found in abdominal abscesses: Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, and Pseudomonas aeruginosa. MB concentration was varied from 50 to 300 μg/mL, and the laser fluence rate was varied from 1 to 4 mW/cm² at a fluence of 7.2 J/cm². Higher fluence rates and fluences were explored for P. aeruginosa. Primary outcomes were the reduction in colony-forming units (CFU) following PDT and measured MB uptake following drug incubation. Gram-positive bacteria (E. faecalis and S. aureus) were eradicated at all MB concentrations and laser fluence rates tested. Efficacy was reduced for E. coli but still resulted in >6 log₁₀ reduction in CFU when MB concentration was at least 100 μg/mL. P. aeruginosa required higher fluence (28.8 J/cm²) to achieve comparable efficacy, while increasing fluence rate did not have a significant effect on PDT efficacy. MB uptake was reduced in Gram-negative species compared to Gram-positive species, particularly P. aeruginosa, although uptake was not significantly correlated with CFU reduction. Gram-positive bacteria can be eradicated in vitro with low levels of MB (50 μg/mL), laser fluence (7.2 J/cm²), and laser fluence rate (1 mW/cm²). E. coli showed substantial cell killing (>6 log₁₀ CFU reduction) with these same parameters. Low MB uptake and PDT efficacy in P. aeruginosa could be overcome by increasing the laser fluence, while increasing fluence rate did not have an effect.