Search Results (56)

Background: Although extensive resection improves the prognosis of gliomas, it risks impairing critical brain functions. Photodynamic therapy (PDT) utilizing talaporfin sodium (TS) targets tumor cells upon light activation. Despite its approval in Japan, TS application remains restricted, and factors influencing its efficacy are unclear. We aimed to identify TS efficacy determinants to optimize treatment outcomes. Methods: Data from 171 patients with grade 4 glioma who underwent surgery and PDT at Tokyo Women’s Medical University Hospital between January 2017 and March 2024 were retrospectively analyzed. Clinical variables evaluated included age, sex, genotype, Karnofsky Performance Status (KPS), serum albumin (Alb) levels, MIB-1 expression levels, and medication history. TS concentrations in tumor tissues were quantitatively assessed in 82 patients (41 primary, 41 recurrent). Survival outcomes were analyzed. RNA-seq was performed on the three highest and three lowest TS concentration samples with significant TS concentration variations to investigate corresponding gene expression changes. Results: Multivariate analysis identified KPS (hazard ratio [95% confidence interval]: 0.96 [0.93–0.99], p = 0.01) and Alb (3.68 [1.05–13.76], p = 0.047) as independent prognostic factors. In recurrent cases, higher TS concentrations were significantly associated with improved survival (p = 0.0454). RNA-seq analysis indicated decreased expression of ACTB and PDPN genes in samples with lower TS concentrations, suggesting potential resistance mechanisms. Conclusions: TS concentration is a critical determinant of PDT efficacy, especially in recurrent glioma, highlighting its prognostic significance. Alb may affect treatment outcomes by mediating TS binding. RNA-seq findings imply that low TS concentrations may suppress immune and stress response-related genes, potentially diminishing PDT sensitivity. Full article

Skin cancer is the world’s fifth most diagnosed malignancy and is increasingly occurring in young adults. The elevated morbidity and mortality of skin cancer are known to be highly correlated with its frequent recurrence after tumor excision. Although regimens such as chemotherapy and/or immunotherapy are often administered following surgical treatments, the patients may suffer from severe side effects, drug resistance, and/or high cost during treatments, indicating that the development of an effective and safe modality for skin cancer after surgery is still highly demanded nowadays. In this study, an injectable and thermoresponsive hyaluronic acid/hexamethylene diisocyanate-Pluronic F127 block copolymer crosslinking composite hydrogel loaded with indocyanine green (ICG) and camptothecin (CPT), called ICHHPG, was developed for photochemotherapy of skin cancer after surgery. ICHHPG can be self-gelationed at 37 °C and stabilizes ICG in the gel matrix. Upon NIR exposure, ICHHPG can generate hyperthermia and consequently provide photothermal therapy when the ICG dosage is >5 μM. Furthermore, ICHHPG may provide a remarkably enhanced cancericidal effect compared to the equal concentration of free ICG (≤10 μM) or CPT (≤1000 μM) alone, and more than 95% of cancer cells can be destroyed as the intra-gel doses of ICG/CPT were elevated to 10/800 μM. Given the confirmed cytotoxicity together with its fluidic and thermoresponsive characteristics which are foreseeably favorable for wound coverage, the developed ICHHPG is highly applicable for use in skin cancer treatment after surgical excision. Full article

Background/Objectives: Diabetes mellitus and periodontitis share a significant, bidirectional relationship. Diabetes raises the risk of periodontitis and influences its severity, impacting tissue repair and bone metabolism. Conversely, periodontal inflammation can disrupt glycemic control, further complicating this interlinked relationship. This systematic review aimed to evaluate the efficacy of antimicrobial photodynamic therapy (aPDT) as an adjunct to subgingival instrumentation (SI) in the treatment of periodontal pockets with a probing pocket depth (PPD) ≥ 5 mm in individuals with type 2 diabetes mellitus (DM2) and periodontitis. Methods: Using the PICOS framework, this review addressed the following question: “How does aPDT as an adjunct to SI compare to SI alone in treating periodontal pockets with PPD ≥ 5 mm in individuals with DM2 and periodontitis?” Databases searched included PubMed, Scopus, and Web of Science up to December 2024. Randomized clinical trials evaluating periodontal status and HbA1c levels in patients with DM2 undergoing periodontal therapy and experiencing SI were included. Patients who received adjunctive aPDT were compared to a control group that received SI alone. A meta-analysis was conducted illustrating treatment effects across groups. Results: After screening 117 studies based on titles and abstracts, three and four studies met the eligibility criteria for quantitative and qualitative analyses, respectively. The principal periodontal parameters assessed included PPD, clinical attachment level (CAL), plaque index (PI), and bleeding on probing (BOP). Forest plots for PD, BOP, PI, and CAL at baseline, three months, and six months revealed no statistically significant differences between the SI+aPDT group and the SI-only group. Glycated hemoglobin across treatment groups was not different. Conclusions: The combination of aPDT with SI provides limited clinical benefits in treating periodontal pockets with a PPD ≥ 5 mm in diabetic patients with periodontitis. Full article

Photodynamic therapy (PDT) has emerged as a promising therapeutic approach owing to its non-invasive nature and minimal toxicity. PDT involves the administration of a photosensitizing agent (PS), which, upon light activation, induces a photodynamic reaction (PDR), leading to targeted cell destruction. However, developing resistance to PDT poses a significant challenge to its effectiveness. Various factors, including properties and administration of PSs, mediate this resistance. Despite the widespread use of substances like 5-aminolevulinic acid (5-ALA) and protoporphyrin, their efficacy is limited due to restricted tumor penetration and a lack of tumor targeting. To address these limitations, nano-delivery techniques and newer PSs like Aza-BODIPY and its derivatives, which offer enhanced tissue penetration, are being explored. In this paper, we provide an overview of resistance mechanisms in PDT and discuss novel methods, substances, and technologies to overcome resistance to improve clinical outcomes in tumor treatment. Full article

Objectives: The aim of this study is to investigate the antimicrobial efficacy of antimicrobial photodynamic therapy (PDT) using natural photosensitizers (curcumin, riboflavin, and phycocyanin) and light-emitting diode (LED) irradiation against multispecies biofilms in an acrylic denture base model. Materials and Methods: Forty-five acrylic specimens were fabricated using heat-curing acrylic resin. The specimens were then infected with a mixed culture of bacterial and fungal species (including Streptococcus mutans, Streptococcus sanguinis, Candida albicans, and Candida glabrata) for 4 days. The acrylic discs were divided into nine groups, with each group containing five discs: control, 0.2% chlorhexidine, 5.25% sodium hypochlorite, curcumin, riboflavin, phycocyanin alone or along with LED. After treatment, the number of colony-forming units (CFUs) per milliliter was counted. In addition, the extent of biofilm degradation was assessed using the crystal violet staining method and scanning electron microscopy. Results: All experimental groups exhibited a significant reduction in colony numbers for both bacterial and fungal species compared to the control (p < 0.001). The PDT groups exhibited a statistically significant reduction in colony counts for both bacteria and fungi compared to the photosensitizer-only groups. Conclusions: The results of this in vitro study show that PDT with natural photosensitizers and LED devices can effectively reduce the viability and eradicate the biofilm of microorganisms responsible for causing denture infections. Full article

Curcumin, a polyphenolic compound derived from Curcuma longa, exhibits significant therapeutic potential in cancer management. This review explores curcumin’s mechanisms of action, the challenges related to its bioavailability, and its enhancement through modern technology and approaches. Curcumin demonstrates strong antioxidant and anti-inflammatory properties, contributing to its ability to neutralize free radicals and inhibit inflammatory mediators. Its anticancer effects are mediated by inducing apoptosis, inhibiting cell proliferation, and interfering with tumor growth pathways in various colon, pancreatic, and breast cancers. However, its clinical application is limited by its poor bioavailability due to its rapid metabolism and low absorption. Novel delivery systems, such as curcumin-loaded hydrogels and nanoparticles, have shown promise in improving curcumin bioavailability and therapeutic efficacy. Additionally, photodynamic therapy has emerged as a complementary approach, where light exposure enhances curcumin’s anticancer effects by modulating molecular pathways crucial for tumor cell growth and survival. Studies highlight that combining low concentrations of curcumin with visible light irradiation significantly boosts its antitumor efficacy compared to curcumin alone. The interaction of curcumin with cytochromes or drug transporters may play a crucial role in altering the pharmacokinetics of conventional medications, which necessitates careful consideration in clinical settings. Future research should focus on optimizing delivery mechanisms and understanding curcumin’s pharmacokinetics to fully harness its therapeutic potential in cancer treatment. Full article

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O₂. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects. In this work, mesoporous titania nanorods were surface-immobilized with Chlorin e6 (Ce6) conjugated through 3-(aminopropyl)-trimethoxysilane as a coupling agent. The mesoporous nanorods act as nano vehicles for doxorubicin delivery, and the Ce6 provides a visible light-responsive production of ROS to induce PDT. The nanomaterials were characterized by XRD, DRS, FTIR, TGA, N₂ adsorption–desorption isotherms at 77 K, and TEM. The obtained materials were tested for their singlet oxygen and hydroxyl radical generation capacity using fluorescence assays. In vitro cell viability experiments with HeLa cells showed that the prepared materials are not cytotoxic in the dark, and that they exhibit photodynamic activity when irradiated with LED light (150 W m⁻²). Drug-loading experiments with doxorubicin (DOX) as a model chemotherapeutic drug showed that the nanostructures efficiently encapsulated DOX. The DOX-nanomaterial formulations show chemo-cytotoxic effects on Hela cells. Combined photo-chemotoxicity experiments show enhanced effects on HeLa cell viability, indicating that the conjugated nanorods are promising for use in combined therapy driven by LED light irradiation. Full article

Oral cancer is the 16th most common malignant tumor worldwide. The risk of recurrence and mortality is high, and the survival rate is low over the following five years. Recent studies have shown that curcumin causes apoptosis in tumor cells by affecting F_oF₁-ATP synthase (ATP synthase) activity, which, in turn, hinders cell energy production, leading to a loss of cell viability. Additionally, irradiation of curcumin within cells can intensify its detrimental effects on cancer cell viability and proliferation (photodynamic therapy). We treated the OHSU-974 cell line, a model for human head and neck squamous cell carcinoma (HNSCC), and primary human fibroblasts. The treatment involved a 1 h exposure of cells to 0.1, 1.0, and 10 μM curcumin, followed or not by irradiation or the addition of the same concentration of pre-irradiated curcumin. Both instances involved a diode laser with a wavelength of 450 nm (0.25 W, 15 J, 60 s, 1 cm², continuous wave mode). The treatment with non-irradiated 1 and 10 µM curcumin caused ATP synthase inhibition and a consequent reduction in the oxygen consumption rate (OCR) and the ATP/AMP ratio, which was associated with a decrement in lipid peroxidation accumulation and a slight increase in glutathione reductase and catalase activity. By contrast, 60 s curcumin irradiation with 0.25 W—450 nm caused a further oxidative phosphorylation (OxPhos) metabolism impairment that induced an uncoupling between respiration and energy production, leading to increased oxidative damage, a cellular growth and viability reduction, and a cell cycle block in the G1 phase. These effects appeared to be more evident when the curcumin was irradiated after cell incubation. Since cells belonging to the HNSCC microenvironment support tumor development, curcumin’s effects have been analyzed on primary human fibroblasts, and a decrease in cell energy status has been observed with both irradiated and non-irradiated curcumin and an increase in oxidative lipid damage and a slowing of cell growth were observed when the curcumin was irradiated before or after cellular administration. Thus, although curcumin displays an anti-cancer role on OHSU-974 in its native form, photoactivation seems to enhance its effects, making it effective even at low dosages. Full article

Extracorporeal photopheresis (ECP) is an apheresis procedure that is conventionally used as a first-line treatment for cutaneous and leukemic subtypes of T-cell lymphoma, such as Sezary’s syndrome and mycosis fungoides. Over the past three decades, its immunotherapeutic properties have been tested on a variety of autoimmune conditions, including many dermatologic diseases. There is ample evidence of ECP’s ability to modify leukocytes and alter cytokine production for certain dermatologic diseases that have been refractory to first-line treatments, such as atopic dermatitis. However, the evidence on the efficacy of ECP for the treatment of these dermatologic diseases is unclear and/or lacks sufficient evidence. The purpose of this paper is to review the literature on the utilization and clinical efficacy of ECP in the treatment of several [autoimmune] dermatologic diseases and discuss its applications, guidelines, recommendations, and future implementation for dermatologic diseases. Full article

Non-melanoma skin cancer (NMSC) is one of the most common types of cancer worldwide. Despite the low mortality rate, rising incidence and recurrence rates are a burden on healthcare systems. Standard treatments such as chemotherapy, radiotherapy, and surgery are either invasive or toxic to healthy tissues; therefore, new, alternative, selective treatments are needed. In this work, a combined photothermal and chemotherapeutic approach is proposed. MoS₂ was used as photothermal agent. It was prepared by a liquid-phase exfoliation and intercalation method using polyvinylpyrrolidone (PVP), followed by recirculation through a custom-built high-power ultrasonication probe. After 6 h of ultrasonication treatment, the average particle size was 165 ± 170 nm. Near-infrared (NIR) irradiation assays (810 nm, 0.1 W/cm², 30 min, 180 J/cm²) confirmed that MoS₂ nanosheets can efficiently convert NIR light into heat and reach 52 °C. The therapeutic doses of MoS₂ (125 µg/mL) and Tegafur (50 µg/mL) were optimized and both were simultaneously incorporated into a Carbopol hydrogel. The cells were brought into contact with the hydrogel and irradiated with a custom-built NIR LED system. In HFF-1 cells (normal human fibroblasts), the metabolic activity was 78% (above the 70% toxicity limit—ISO 10993-5:2009(E)), while in A-431 skin cancer cells, it was 28%. In addition, the MoS₂ + Tegafur hydrogels led to a 1.9-fold decrease in A-431 cancer cell metabolic activity, 72 h after irradiation, in comparison to MoS₂ hydrogels, indicating a combined effect of photothermal and chemotherapy. Full article

[Ru(bipy)₂(dpphen)]Cl₂ (where bipy = 2,2′-bipyridine and dpphen = 2,9-diphenyl-1,10-phenanthroline) (complex 1) is a sterically strained compound that exhibits promising in vitro photocytotoxicity on an array of cell lines. Since lung adenocarcinoma cancer remains the most common lung cancer and the leading cause of cancer deaths, the current study aims to evaluate the plausible effect and uptake of complex 1 on human alveolar carcinoma cells (A549) and mesenchymal stem cells (MSC), and assess its cytotoxicity in vitro while considering its effect on cell morphology, membrane integrity and DNA damage. MSC and A549 cells showed similar rates of complex 1 uptake with a plateau at 12 h. Upon photoactivation, complex 1 exhibited selective, potent anticancer activity against A549 cells with phototoxicity index (PI) values of 16, 25 and 39 at 24, 48 and 72 h, respectively. This effect was accompanied by a significant increase in A549-cell rounding and detachment, loss of membrane integrity and DNA damage. Flow cytometry experiments confirmed that A549 cells undergo apoptosis when treated with complex 1 followed by photoactivation. In conclusion, this present study suggests that complex 1 might be a promising candidate for photochemotherapy with photoproducts that possess selective anticancer effects in vitro. These results are encouraging to probe the potential activity of this complex in vivo. Full article

Objectives: This study investigates the efficacy of antimicrobial photodynamic therapy (aPDT) using riboflavin and a blue diode laser (BDL), combined with shock wave-enhanced emission photoacoustic streaming (SWEEPS), against Enterococcus faecalis. Materials and Methods: A total of 48 extracted single-rooted human teeth were used. The root canals were instrumented, sealed at their apices, had the smear layer removed, and then underwent autoclave sterilization. Subsequently, each canal was inoculated with E. faecalis bacterial suspension and allowed to incubate for ten days. After confirming the presence of biofilms through scanning electron microscopy (SEM) in three teeth, the remaining teeth were randomly allocated into nine groups, each containing five teeth: control, 5.25% sodium hypochlorite (NaOCl), BDL, SWEEPS + normal saline, SWEEPS + NaOCl, riboflavin, riboflavin + SWEEPS, riboflavin + BDL, and riboflavin + BDL + SWEEPS. After the treatment, the numbers of colony-forming units (CFUs)/mL were calculated. The data were analysed using one-way ANOVA followed by Tukey’s test for comparisons. Results: All groups, with the exception of the BDL group, exhibited a significant reduction in E. faecalis CFU/mL when compared to the control group (p < 0.001). The difference in CFU/mL value between riboflavin + BDL + SWEEPS and riboflavin + SWEEPS was significant (p = 0.029), whereas there was no significant difference between riboflavin + BDL + SWEEPS and riboflavin + BDL (p = 0.397). Moreover, there was no statistically significant difference between the riboflavin + SWEEPS group and the riboflavin + BDL group (p = 0.893). Conclusions: The results demonstrated that combining the SWEEPS technique with riboflavin as a photosensitizer activated by BDL in aPDT effectively reduced the presence of E. faecalis in root canals. Full article

Breast cancer is one of the most common cancers among women. The development of new and effective therapeutic approaches in the treatment of breast cancer is an important challenge in modern oncology. Two-dimensional (2D) cell cultures are most often used in the study of compounds with potential anti-tumor nature. However, it is necessary to develop advanced three-dimensional (3D) cell models that can, to some extent, reflect the physiological conditions. The use of miniature cancer-on-a-chip microfluidic systems can help to mimic the complex cancer microenvironment. In this report, we developed a 3D breast cancer model in the form of a cell multilayer, composed of stromal cells (HMF) and breast cancer parenchyma (MCF-7). The developed cell model was successfully used to analyze the effectiveness of combined sequential photochemotherapy, based on doxorubicin and meso-tetraphenylporphyrin. We proved that the key factor that allows achieving the synergistic effect of combination therapy are the order of drug administration to the cells and the sequence of therapeutic procedures. To the best of our knowledge, studies on the effectiveness of combination photochemotherapy depending on the sequence of the component drugs were performed for the first time under microfluidic conditions on a 3D multilayered model of breast cancer tissue. Full article

Background: Persistent bacterial infections caused by biofilm-associated Enterococcus faecalis are a global public health concern. This study aims to compare the biofilm removal effects of methylene blue (MB) or hydrogen peroxide (HP) mediated photodynamic inactivation (PDI) with a shock wave enhanced emission photoacoustic streaming (SWEEPS) method laser irradiation enhanced bactericidal activity. Methods: A total of fifty extracted single-rooted human teeth were used. Each canal was then inoculated with a bacterial suspension of E. faecalis and left for ten days to induce biofilm formation. The antibacterial effects within treated root canals using MB or HP + diode laser or SWEEPS alone or in combination were assessed and compared with 5.25% sodium hypochlorite (NaOCl) as the positive control group. Data were analyzed using one-way ANOVA and Tukey’s post hoc test. Results: The MB + diode laser + SWEEPS and HP + diode laser + SWEEPS groups displayed significantly lower amounts of bacteria than either the MB + diode laser or SWEEPS and HP + diode laser or SWEEPS groups (p < 0.001). There was no statistically significant difference detected between the diode laser and SWEEPS groups (p = 0.982). Conclusions: SWEEPS can enhance the photosensitizer distribution in the root canal, leading to effective biofilm removal. This technique could thus help promote the future development of endodontic treatments. Full article

Nanodelivery systems combining photothermal therapy (PTT) and chemotherapy (CT), have been widely used to improve the efficacy and biosafety of chemotherapeutic agents in cancer. In this work, we constructed a self-assembled nanodelivery system, formed by the assembling of photosensitizer (IR820), rapamycin (RAPA), and curcumin (CUR) into IR820-RAPA/CUR NPs, to realize photothermal therapy and chemotherapy for breast cancer. The IR820-RAPA/CUR NPs displayed a regular sphere, with a narrow particle size distribution, a high drug loading capacity, and good stability and pH response. Compared with free RAPA or free CUR, the nanoparticles showed a superior inhibitory effect on 4T1 cells in vitro. The IR820-RAPA/CUR NP treatment displayed an enhanced inhibitory effect on tumor growth in 4T1 tumor-bearing mice, compared to free drugs in vivo. In addition, PTT could provide mild hyperthermia (46.0 °C) for 4T1 tumor-bearing mice, and basically achieve tumor ablation, which is beneficial to improving the efficacy of chemotherapeutic drugs and avoiding damage to the surrounding normal tissue. The self-assembled nanodelivery system provides a promising strategy for coordinating photothermal therapy and chemotherapy to treat breast cancer. Full article