Search

• This retrospective study compared the outcomes of ALA PDT and observation only of LSIL patients with HR-HPV infection. • Spontaneous HPV clearance and lesion regression could occur in > 50 % patients within 2 years without intervention. • Quicker and higher LSIL remission rate and HR-HPV negative conversion rate could be achieved after multiple ALA PDT treatments. Prevention of high-risk HPV (HR-HPV) infection and effective medical intervention of persistent HPV infection and precancerous lesions are critical for the prevention of cervical cancer. The aim of this retrospective comparative study was to evaluate the outcomes of ALA PDT and observation only in the management of low-grade squamous intraepithelial lesions (LSIL). In PDT Group (n = 138), ALA PDT was applied to patients with colposcopic biopsy confirmed cervical LSIL accompanied with HR-HPV infection longer than 1 year or HPV 16/18 subtype infection. Cervical LSIL only patients received 3 times of ALA PDT and those with concurrent cervical canal or vaginal lesions received 6 times ALA PDT. Control Group (n = 69) received observation only. Colposcopy, TCT and HPV typing were performed before and after treatment. Patients were followed up for up to two years. The observation group showed 26.1%, 34.8% and 53.6% HR-HPV negative conversion at 3-6, 12 and 24 months, respectively. LSIL regression rate of the observation group was 33.33%, 36.23% and 65.22% at 3-6, 12 and 24 months, respectively. There was 62.32%, 80.56% and 89.22% patients achieved HPV clearance at 3-6, 12 and 24 months after PDT treatment, respectively. The LSIL remission rate was 89.86%, 94.40% and 96.08% at 3-6, 12 and 24 months after ALA PDT, respectively. The abnormal TCT (≧ ASCUS) was reduced from 92% to 10.1%, 4.6% and 3.9% at 3-6, 12 and 24 months after ALA PDT, respectively. The patient age was not a factor affecting the clearance of HPV infection and the LSIL regression rate of PDT treatment. This study demonstrates that the application of multiple ALA PDT treatments has added value in achieving both short-term and long-term HPV and lesion clearance. [ABSTRACT FROM AUTHOR]

• Photodynamic therapy (PDT) might improve healing rates for diabetic foot ulcers (DFUs) compared to standard care (SOC). • The meta-analysis of 6 RCTs involving 458 patients showed no significant difference in ulcer size reduction between PDT and SOC. • PDT significantly increased wound healing rates without a corresponding increase in complications. • No significant difference in pain levels between the PDT and SOC treatment groups was observed. Diabetic foot ulcer (DFU) is a chronic and challenging condition, addressed through various treatments including photodynamic therapy (PDT) and standard of care (SOC), yet lacking consensus on the optimal approach. This study presents a comprehensive meta-analysis of randomized controlled trials to evaluate the efficacy and safety of PDT versus SOC in managing DFU. An extensive literature search was conducted across PubMed, Embase, and the Cochrane Library databases to identify RCTs that compared the effectiveness of PDT with SOC in treating DFU. The primary metrics evaluated included changes in ulcer area, wound healing indices, and pain levels experienced by the patients. This meta-analysis incorporated data from 6 RCTs, encompassing 458 patients with 467 DFUs. The analysis indicated that while PDT led to a faster reduction in ulcer size compared to SOC, the difference was not statistically significant [mean difference (MD): 2.73cm², 95 % Confidence Interval (CI) -2.98 to 8.44; p > 0.05]. However, a notable improvement was observed in the wound healing rate in the PDT group [MD: 29.26 %, 95 % CI 7.24 to 51.28; p = 0.01]. Based on the Visual Analog Scale (VAS), pain assessment revealed no significant difference between the two treatment groups [MD: 2.35, 95 % CI -2.36 to 7.06; p = 0.33]. The study suggests that PDT might offer an enhanced healing rate for DFUs compared to SOC alone, potentially leading to improved patient outcomes. Importantly, our findings highlight the superiority of photodynamic therapy in accelerating ulcer healing without an associated increase in complications. 2023 CRD42023493930 [ABSTRACT FROM AUTHOR]

• We performed PDT for tumors > 2 cm in diameter. • Stable disease or better was observed over long-term follow up. • PDT can inhibit tumor progression in the long term. • We dubbed this type of PDT "maintenance PDT". Photodynamic therapy (PDT) is used for the treatment of centrally-located early lung cancers (CLELCs) and is recommended for tumors ≤ 1.0 cm in diameter. We previously reported that PDT using talaporfin sodium, second-generation photosensitizer, for tumors > 1.0 cm but ≤ 2.0 cm in diameter was able to achieve a therapeutic outcome comparable to that of tumors with a diameter of ≤ 1.0 cm. However, the effectiveness of PDT using talaporfin sodium for tumors > 2.0 cm in diameter remains unclear. We conducted a retrospective analysis of cases in which PDT was performed for flat-type CLELCs with tumor diameters of > 2.0 cm. We retrospectively analyzed seven cases (eight lesions) with tumor diameters > 2.0 cm and no evidence of extracartilaginous invasion or lymph node metastasis. All the patients underwent multiple PDT sessions. The PDT treatment results over the study period were partial response in one case (14.3 %), stable disease (SD) in three cases (42.9 %), and progressive disease (PD) in three cases (42.9 %). At the time of writing this report, five of seven cases (71.4 %) are still undergoing treatment. The duration of SD—the time from the start of treatment until the criteria for PD were met (SD or better maintained)—ranged from 7 to 52 months (mean, 25.3 months). "Maintenance PDT" for CLELCs > 2.0 cm in diameter has the potential to inhibit tumor progression in the long term while maintaining quality of life, rather than simply aiming only for a quick radical cure. [ABSTRACT FROM AUTHOR]

• Novel in vitro model of recurrent DFSP established for therapeutic evaluation. • Significant anti-tumor efficacy against DFSP model by 5-ALA PDT. • Inhibition of DFSP cell viability and induction of apoptosis by 5-ALA PDT. • Suppression of DFSP cell migration, invasion, and angiogenic potential by 5-ALA PDT. • Downregulation of key DFSP-related genes COL1A1 and PDGFRB by 5-ALA PDT. Dermatofibrosarcoma Protuberans (DFSP) is a rare, low-grade malignant tumor of the dermis with a high recurrence rate post-surgery. Current treatments, including surgery, radiotherapy, and targeted therapy, have limitations. Photodynamic therapy (PDT) with 5-aminolevulinic acid (5-ALA) is a promising non-invasive approach, but its efficacy in DFSP treatment remains underexplored. This study aimed to evaluate the anti-tumor efficacy of 5-ALA PDT using an in vitro model derived from a recurrent DFSP patient. The cells were treated with varying concentrations of 5-ALA and exposed to red light, followed by assessments of cell viability, proliferation, apoptosis, migration, invasion, angiogenesis, and expression of DFSP-related genes and proteins. 5-ALA PDT significantly reduced DFSP cell viability in a dose-dependent manner and induced apoptosis. It also effectively inhibited cell proliferation, migration, and invasion, as well as suppressed angiogenic activity in conditioned media. Furthermore, 5-ALA PDT downregulated the expression of COL1A1 and PDGFRB, key genes in DFSP pathogenesis. The findings provide the first evidence of 5-ALA PDT's in vitro anti-tumor efficacy against DFSP, suggesting its potential as a novel therapeutic approach for DFSP. Further studies are warranted to explore the clinical utility of 5-ALA PDT in preventing DFSP recurrence. [ABSTRACT FROM AUTHOR]

• Cervical and vaginal giant condylomata acuminata with high-risk subtypes of the human papillomavirus (HPV) infection and low-grade squamous intraepithelial lesions is rare and difficult to treat. • The combination of Holmium yttrium aluminum garnet (Ho: YAG) laser and photodynamic therapy with a derivative of chlorin e6 (Ce6) photosensitizer (STBF) successfully treated cervical and vaginal giant CA and LSIL with mild adverse reactions. • Ho: YAG laser combined with STBF-PDT is a promising approach for refractory HPV infected diseases, especially for special cervical and vaginal fornix areas. Photodynamic therapy (PDT) is proved effective for treating low-grade squamous intraepithelial lesions (LSIL) and condylomata acuminata (CA). 5-Aminolevulinicacid (5-ALA) is the most common applied photosensitizer, but high rate of unbearable pain and relative long incubation time were reported. Here, we report a 27-year-old woman suffering from cervical and vaginal giant CA with LSIL involving the whole right vaginal fornix, cervical surface, and vaginal wall. Holmium yttrium aluminum garnet (Ho: YAG) laser was first applied to remove the giant CA lesions. STBF, a derivative of chlorin e6 (Ce6) was then applied on suspicious lesions as a new photosensitizer for 1 h. Lesions were exposed to LED illumination with a wavelength of 630 nm and light dose of 200–284 J/cm2 for cervical canal and the vaginal surfaces, 100–150 J/cm2 for cervix surface. Vaginal giant CA and LSIL lesions got complete remission at 6-month follow-up. Mild tolerable adverse reactions were observed after STBF-PDT and relieved in 24 h. Thus, the combination of Ho: YAG laser and STBF-PDT may be a novel option for cervical and vaginal giant CA and LSIL, especially for special vaginal fornix areas. [ABSTRACT FROM AUTHOR]

• A prospective, split-face, randomized controlled trial. • Intense pulsed light-photodynamic therapy(IPL-PDT)is a more effective method than IPL in the treatment of seborrhea, as well as on the improvement of the skin barrier function. • The adverse effects of IPL-PDT are similar to those of IPL, which are mild to moderate local reactions. Seborrhea poses a common cosmetic concern in adolescents and young adults, often accompanied by enlarged pores, and contributing to various skin conditions, including acne vulgaris and seborrheic dermatitis. At present, there is a lack of effective treatment for this problem, and the potential of photodynamic therapy (PDT) in reducing sebum remains inconclusive. This exploratory, prospective, single-center, double-blinded, randomized split-face controlled trial aimed to compare the efficacy and safety of intense pulsed light-photodynamic therapy (IPL-PDT) versus IPL therapy for seborrhea. Participants with seborrhea underwent 3 times of IPL treatment (590 nm, 15–17 J/cm2 based on patient's tolerance) for one hemifacial part and IPL-PDT treatment for the other. Follow-up assessment was conducted up to 8 weeks after the final treatment. Compared with single IPL treatment, IPL-PDT can significantly inhibit sebum secretion and decrease pore size. PDT group exhibited no additional damage to the skin barrier, with even lower transepidermal water loss (TEWL). Additionally, the PDT group showed superior improvement in scores of porphyrins, red areas, and ultraviolet (UV) spots. Both groups experienced only mild topical adverse effects, well tolerated by the participants. IPL-PDT is a more effective method than IPL in the treatment of seborrhea, as well as on the improvement of the skin barrier function. [ABSTRACT FROM AUTHOR]

• Highly expressed MTH1 and the failure of ROS generation lead to PDT resistance in lung cancer cells. • CEP treatment enhances ROS generation, damages DNA and thereby further promotes MTH1 expression. • The combination of CEP and PDT induces robust DNA damage, making DNA irreparable and down-regulating MTH1, leading to cell death thereupon. Photodynamic therapy (PDT) primarily treats skin diseases or cancer by generating reactive oxygen species (ROS) to damage cellular DNA, yet drug resistance limits its application. To tackle this problem, the present study was carried out to improve the efficacy of chlorin e6 (Ce6)-PDT using Cepharanthine (CEP) as well as to reveal the potential molecular mechanism. Lewis lung cancer cell line (LLC) was utilized as the cancer cell model. chlorin e6 (Ce6) acted as the photosensitizer to induce PDT. The in vitro anti-cancer efficacy was measured by CCK-8, Annexin-V/PI staining, and migration assay. The Ce6 uptake was observed using flow cytometry and confocal microscopy. The ROS generation was detected by the DCFH-DA probe. The analysis of MutT Homolog 1 (MTH1) expression, correlation, and prognosis in databases was conducted by bioinformatic. The MTH1 expression was detected through western blots (WB). DNA damage was assayed by WB, immunofluorescent staining, and comet assay. Ce6-PDT showed robust resistance in lung cancer cells under certain conditions, as evidenced by the unchanged cell viability and apoptosis. The subsequent findings confirmed that the uptake of Ce6 and MTH1 expression was enhanced, but ROS generation with laser irradiation was not increased in LLC, which indicated that the ROS scavenge may be the critical reason for resistance. Surprisingly, bioinformatic and in vitro experiments identified that MTH1, which could prevent the DNA from damage of ROS, was highly expressed in lung cancer and thereby led to the poor prognosis and could be further up-regulated by Ce6 PDT. CEP exhibited a dose-dependent suppressive effect on the lung cancer cells. Further investigations presented that CEP treatment boosted ROS production, thereby resulting in DNA double-strand breakage (DDSB) with activation of MTH1, indicating that CEP facilitated Ce6-PDT-mediated DNA damage. Finally, the combination of CEP and Ce6-PDT exhibited prominent ROS accumulation, MTH1 inhibition, and anti-lung cancer efficacy, which had synergistic pro-DNA damage properties. Collectively, highly expressed MTH1 and the failure of ROS generation lead to PDT resistance in lung cancer cells. CEP facilitates ROS generation of PDT, thereby promoting vigorous DNA damage, inactivating MTH1, alleviating PDT resistance, and ameliorating the anti-cancer efficacy of Ce6-PDT, provides a novel approach for augmented PDT. [Display omitted] [ABSTRACT FROM AUTHOR]

• DTPP is a novel photosensitizer DTPP with a chemical name of 5–5- (4-N, N-diacetoxylphenyl)−10,15,20- tetraphenylporphyrin. It is a derivative of second-generation porphyrin compounds. • Morphologic observation and apoptosis, reactive oxygen species (ROS) level, antioxidant indices, nitric oxide (NO) content, mitochondrial membrane potential (MMP), and apoptosis-related protein levels Caspases- 9, Caspases-3, cytochrome c, Bcl- 2, Bax, etc. were determined to clarify the mechanism of PDT. • 2-DE and protein identification by MALDI-TOF-MS was successfully prepared and our results indicate that the mechanism of DTPP-PDT on lung cancer was as follows: mitochondrial cytochrome c is released into the cytoplasm, then Caspases-9 /Caspases-3 was activated and Bcl-2 decreased/Bax increases, thus initiated the cell apoptosis. • DTPP-PDT could induce oxidative stress and apoptosis via the mitochondrial pathway in LA795 cells. • These findings are novel and offer a promising system for lung cancer treatment. Investigation of the effects of 5–5- (4-N, N-diacetoxylphenyl)-10,15,20- tetraphenylporphyrin (DTPP)-mediated photodynamic therapy (PDT) on oxidative stress and mitochondrial apoptosis in LA795 lung cancer cells. Proteomics was used to identify differentially expressed proteins after PDT treatment. The apoptosis rate was determined by flow cytometry. Morphologic observation of apoptosis, reactive oxygen species (ROS) levels, antioxidant indices, nitric oxide (NO) content, mitochondrial membrane potential (MMP), and Caspase- 9 and Caspase-3 were determined by assays; apoptosis-related protein levels of Cytochrome (Cyto) c, Bcl- 2, Bax were determined by Western blot. Typical apoptosis morphology of LA795 cells was observed after PDT. The cells were mainly in the apoptosis death pathway with high cell apoptosis rates. The proteomics study observed the apoptosis-associated proteins, oxidative stress proteins, antioxidant proteins, the cytoskeletal protein and mitochondrial dysfunction in LA 795 cells. Additional results indicated that PDT could increase levels of ROS, NO; decrease glutathione (GSH) content and MMP; upregulated Bax, Cyto c, and Caspase-3 protein expression, inhibited Bcl-2 protein expression, and further induced cell apoptosis. The effect of DTPP-PDT on lung cancer was: first, mitochondrial Cyto c is released into the cytoplasm, then Caspase- 9 / Caspase-3 was activated, Bcl-2 decreased/Bax increased, initiating cell apoptosis. DTPP-PDT could induce oxidative stress and apoptosis via mitochondrial pathways in LA795 cells. [ABSTRACT FROM AUTHOR]

• This paper shows for the first time the efficacy of PDT with BF-200 ALA in successfully treating keratinocyte neoplastic lesions in long-term immunosuppressed patients. • The usage of PDT for actinic keratosis, Bowen's disease and basal cell carcinoma in immunosuppressed patients is safe and with mild adverse effects that do not differ from those seen in immunocompetent patients. • PDT with BF-200 ALA adds to the list of efficacious and safe options to treat keratinocyte neoplastic lesions in immunosuppressed patients. Continuous immunosuppression after organ transplantation is associated with an increased risk of developing keratinocyte neoplastic lesions. Topical photodynamic therapy represents a therapeutic approach for different keratinocyte neoplastic lesions. However, the specific efficacy and safety of this treatment in this immunocompromised population remains largely unknown. In this case report series, we show the efficacy and safety of photodynamic therapy with BF-200 ALA gel using red-light and daylight in immunocompromised patients. Out of 8 patients presented here, 1 was treated for 8 basal cell carcinomas, 1 for 2 Bowen´s disease lesions and 6 were treated for field cancerization including 4 to 10 actinic keratoses. Treatment response rates were above 75 %. The adverse events, including pain, did not differ from those already described for PDT. These data suggest that PDT with BF-200 ALA gel could be an effective and safe option to add to the treatment portfolio for neoplastic keratinocyte lesions in this high-risk population. [ABSTRACT FROM AUTHOR]

• The degree of apoptosis and the expression of apoptotic molecules is related to the prognosis of NSCLC-PDT. • The best anti-tumor effect caused by the optimal light dose of PDT may be driven by pro-apoptotic mechanisms. • Adjusting light dosimetry optimizes PDT-induced cell apoptosis and inhibits tumor growth maximally at least in the preclinical system. Photodynamic therapy (PDT) is receiving increasing attention in treating non-small cell lung cancer (NSCLC) worldwide, but in clinical practice, the relationship between treatment effect and PDT light dose in NSCLC remains unclear. Therefore, we aimed to determine the optimal light dose for PDT by exploring molecular biomarkers and evaluating tumor growth data. We applied bioinformatics to identify promising genes and pathways in NSCLC and PDT. Then, the human lung adenocarcinoma cell line A549-bearing BALB/c nude mice were treated with hematoporphyrin derivative (HPD, 3 mg/kg) that is currently used widely for lung cancer treatment in the world even with photosensitization issues. After 48 h, tumor-bearing mice were irradiated superficially at doses of 100, 200, 300, 400, and 500 J/cm2. The tumor growth data and apoptotic molecules were assessed and calculated. Bioinformatics results indicated that the apoptosis pathway was significantly enriched and caspase 3 was the most promising biomarker on prognosis in NSCLC-PDT. Compared to the untreated group, there was no difference in the relative tumor volume (RTV) of the 100 J/cm2 group, while the RTV of the other treatment groups (200–500 J/cm2) was significantly lower. In the 100 J/cm2 group, there were significant differences in the complete remission (CR, 0 %) and the percentage of tumor growth inhibition rate (TGI%) over 75 % (20 %) compared with the other treatment groups, especially the 300 and 400 J/cm2 groups (CR 70 %; TGI% 90 %). In the 300 and 400 J/cm2 groups, the expression of caspase 3, cleaved-caspase 3, PARP1, and Bax was increased significantly, while Bcl-2 expression was significantly lower. Moderate doses of PDT (300 or 400 J/cm2) are more effective than low (100 or 200 J/cm2) or high doses (500 J/cm2) in the A549 tumor-bearing mice model. Since the A549 tumor is more akin to human tumors in pathological behavior, these experimental data may contribute to improving HPD-PDT illumination protocols for favorable clinical outcomes. [ABSTRACT FROM AUTHOR]

• After three HMME-PDT sessions, cure rate and effective rate were 12.80 % and 32.50 %, respectively. • Therapeutic effects are influenced by age, subtype, and site, but not the gender. • Compared to patients under the age of 15, patients aged 21–30 were found to have a 3.4-fold higher likelihood of undergoing HMME-PDT under general anesthesia. To conduct a retrospective analysis of Hemoporfin photodynamic therapy (HMME-PDT) in the treatment of port-wine stains (PWS). A retrospective analysis was conducted based on the clinical data from March 2017 to December 2022, so as to summarize the demographic characteristics, clinical efficacy and adverse reactions. The effectiveness of HMME-PDT was examined with respect to treatment times, age, gender, subtype, and location of PWS lesions. The age of the 2952 cases ranged from 8 months to 56 years old (median, 2.8 years), with 1419 males (48.07 %), and 1533 females (51.93 %). There were 669 cases of pink type (22.66 %), 2184 cases of purplish red type (73.98 %), and 99 cases of nodular thickening type (3.35 %). The prevalence location was face (88.04 %), neck (14.94 %), limbs and trunk. 1602 cases (54.27 %) had never received treatment, 661 cases (22.39 %) had been treated by pulse dye laser (PDL), 229 cases (7.76 %) had previously been treated by PDT, 296 cases (10.03 %) had received both the modalities. The 2952 cases completed totally 7996 HMME-PDT times. Cure rate and effective rate increased continuously with the number of treatments. The pink type has the highest cure rate and effective rate, followed by the purplish red type and the last was the nodular thickening type. The therapeutic effects are considerably influenced by age, subtype, and treatment site (P < 0.05). However, there was no significant difference in the effectiveness of HMME-PDT between both genders. The local adverse reactions after the first treatment included edema (97.73 %), itching (82.62 %), purpura-like change (79.51 %), crusts (24.59 %), infection (4.07 %), scars (1.08 %), hyperpigmentation (0.61 %), and depigmentation (0.41 %). Nausea and vomiting occurred in 2 juveniles and 1 young adult (5, 6 and 22 years old respectively) immediately after treatment, and did not interfere with the administration of the treatment. Patients aged 21–30 were found to have a 3.4-fold higher likelihood of undergoing HMME-PDT under general anesthesia compared to those aged 15 or younger. There was no distinct systemic adverse reaction, such as allergic responses, cardiovascular effects, neurological symptoms, hematological abnormalities, respiratory symptoms, or musculoskeletal issues. HMME-PDT is preferred in treating PWS, with relatively high effective rate and cure rate, mild local reactions and no distinct systemic adverse reaction. [ABSTRACT FROM AUTHOR]

• Characterize and test the Ultrasonic Photodynamic Inactivation Device" (UPID). • Antimicrobial inactivation and disinfection action of solid surfaces using PID. • Action of microbial inactivation against gram-positive, gram-negative bacteria and yeast. • Propose a low cost and atoxic alternative for microbial control of surfaces of acrylic, titanium. • Propose an alternative for surgical instruments, aesthetic, laboratories and industries. Photodynamic Therapy (PDT) is an alternative to surface decontamination that is based on the interaction between a non-toxic photosensitizer (PS) and a light source to allow for the formation of reactive oxygen species. The objective of this study was to test a new patented device - the "Ultrasonic Photodynamic Inactivation Device" (UPID) under the patent deposit MU-BR 20.2018.00.9356-3 - for the photodynamic inactivation on contaminated acrylic plates and titanium disk. This new low cost device contains light emitting diodes (LEDs) and was built in a stainless-steel container for better light distribution. In addition, 28 waterproof red LEDs plates, with a wavelength of 660 nm were used, containing three irradiators in each plate, for which the irradiation distribution and the spectral irradiance on all 6 internal faces of this device were calculated. The effect of red LED irradiation (660 nm) methylene blue (MB) (100 μmol/L) diluted in water or 70% alcohol on three types of microorganisms: Candida albicans ATCC 10231, Staphylococcus aureus ATCC 25923 and Escherichia coli ATCC 25922. In order to estimate the effects of PDI, acrylic plates and Titanium disks were contaminated by bacterial suspensions (3 × 108 CFU/mL), then treated with a solution of MB for 30 min, followed by irradiation for 30 min (0.45 J/cm2). Microbial inhibition was evaluated by counting the number of colony forming units (CFU), compared to the control group. The results showed that the UPID promoted significant reduction (p < 0.001) of the microorganism when compared with the positive control. The new device promoted an effective microbial inhibition on the surfaces tested and, thus, makes possible new studies. The perspective is that this new device may be a low-cost and non-toxic alternative to the disinfection of biomedical devices, non-critical instruments and also for use in the food industry. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • A new combined iron chelating prodrug (AP2-18) has been synthesised and evaluated. • AP2-18 significantly increased protoporphyrin IX accumulation in human skin cells. • This enhancement translated into greater cytotoxicity on irradiation. • Clinical AP2-18 application may improve future dermatological photodynamic therapy. Abstract Background Photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of cancers and precancers. It is particularly useful in its topical form in dermatology but improvement of efficacy is required to widen its application. Methods An ester between aminolaevulinic acid (ALA) and CP94 was synthesised (AP2-18) and experimentally evaluated to determine whether protoporphyrin IX (PpIX)-induced PDT effectiveness could be improved. A biological evaluation of AP2-18 was conducted in cultured human primary cells with both PpIX fluorescence and cell viability (as determined via the neutral red assay) being assessed in comparison to the PpIX prodrugs normally utilised in clinical practice (aminolaevulinic acid (ALA) or its methyl ester (MAL)) either administered alone or with the comparator iron chelator, CP94. Results No significant dark toxicity was observed in human lung fibroblasts but AP2-18 significantly increased PpIX accumulation above and beyond that achieved with ALA or MAL administration +/- CP94 in both human dermal fibroblasts and epithelial squamous carcinoma cells. On light exposure, the combined hydroxypyridinone iron chelating ALA prodrug AP2-18 generated significantly greater cytotoxicity than any of the other treatment parameters investigated when the lowest concentration (250 μM) was employed. Conclusions Newly synthesised AP2-18 is therefore concluded to be an efficacious prodrug for PpIX-induced PDT in these dermatologically relevant human cells, achieving enhanced effects at lower concentrations than currently possible with existing pharmaceuticals. [ABSTRACT FROM AUTHOR]

The pilot study was performed to assess the usefulness of a newly developed patientand physician-friendly intravaginal irradiation system for photodynamic therapy with 5-aminolevulinic acid (5-ALA PDT) for cervical intraepithelial neoplasia (CIN). We used an intravaginal balloon applicator to make the cervix upright and to adjust the position and direction of the laser source in the vagina, resulting in minimal patient discomfort and minimal effort required by the physician during irradiation. Ten outpatients of CIN2 or 3 with high-risk human papillomavirus (HPV) infection without a history of HPV vaccination were treated by 5-ALA PDT. Each patient underwent PDT four times every two weeks. Nine patients showed pathological improvement, and the HPV clearance rate was 80%, and no recurrence was observed at two-years follow-up. Serum anti-HPV16 antibodies were detected in seven patients, and the antibody levels of three patients were high, equivalent to those acquired after HPV vaccination. Our newly developed irradiation system enabled easy repeat 5-ALA PDT in the outpatient clinic resulting in the improvement of CIN lesions and HPV clearance. Our results also suggested that repeated 5-ALA PDT might enhance HPV antibody production in CIN patients. [ABSTRACT FROM AUTHOR]

Highlights • Synthesis of iron nanoparticles coated by Gallic acid and encapsulated Indocyanine Green using Co-precipitation method. • Analyzing the release rate based on variations in pH and time. • SGI was studied on the account of its potential for PDT/PTT. • The conjugated provided synergism between PDT and PTT. So, it is suggested to consider as an effective agent for PTT/PDT. • 730 nm non-coherent light exposure did not have any effect on cell death, but was effective in the presence of conjugated. Abstract Background In this study, iron oxide nanoparticles (SPIONs) were synthesized and coated by GA (SG) and then SG was encapsulated by ICG (SGI). After identifying specifications and cytotoxicity of the agents, the potential of SGI for photodynamic therapy (PDT) and photothermal therapy (PTT) was studied. Methods An SGI size of 12–13 nm was determined by TEM images and its zeta potential was measured at −23.8 ± 5.8 mV. MCF-7 and HT-29 cells were exposed to a non-coherent light source at a wavelength of 730 nm and a range of 3.9–124.8 J/cm2 under two different concentrations of agents. The viability of treated cells was determined via MTT assay. To analyze the effects of different irradiation conditions, some indices such as Coefficient of Light Effect, Synergism Index, Addition Ratio, Treatment Efficacy and ED 50 were defined. Results Cell survival at the highest power of irradiation in the absence of any agent was decreased to 93% and 73% for HT-29 and MCF-7, respectively. In both cell lines, the cellular survival dropped by increasing the light source intensity. The maximum cell death recorded for SG, ICG and SGI was 63 ± 2%, 63 ± 2% and 21 ± 2% for MCF-7 cells and 67 ± 2%, 78 ± 1% and 53 ± 1% for HT-29 cells, respectively. Conclusion SGI had a significant photodynamic and photothermal effect on cells. This is a promising outcome, which can help enhance the effectiveness of a minimally invasive treatment. Moreover, SPIONs can be used to apply magnetic hyperthermia or act as a contrast agent in MRI images. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Increasing resistance to antibiotics is one of the most urgent challenge in medicine. • Preclinical and clinical trials of PDI against wound infections are described. • PDI offers an alternative for combating the microbial resistance in the infected leg ulcers. • PDI can heal infected leg ulcers completely and improves a patient’s quality of life. • Combination of nanomaterials and inorganic salts potentiate PDI outcome. Abstract Infected leg ulcers are painful, debilitating and reduce a patient’s quality of life, therefore they are becoming a significant clinical and socioeconomic problem. Increasing resistance to antibiotics, is one of the most urgent challenge to medicine worldwide and requires searching for new, innovative and more efficient medical strategies. One of the opportunities for the cure of leg ulcers is photodynamic inactivation (PDI), which has been widely used in the treatment of various bacterial, fungal and viral infections. PDI encompasses three independently non-toxic elements: a photosensitizer (PS), light of an appropriate wavelength, and molecular oxygen that lead to generation of reactive oxygen species (ROS) responsible for inactivation of microorganisms, including those present in the form of biofilm in chronic wounds. PDI, due to its multiple mechanism of action, low invasiveness and lack of significant side effects, offers an interesting potential alternative for combating the microbial resistance in the infected leg ulcers. It also significantly decreases the area of leg ulcers, or may even heal them completely and thus remarkably improves a patient’s health. [ABSTRACT FROM AUTHOR]

Abstract Purpose We explored the protective effects of N -acetylcysteine (NAC) on chorioretinal damage induced by photodynamic therapy (PDT) in an experimental rat model of choroidal neovascularization (CNV). Methods Experimental CNV was induced by an argon laser in 24 Brown Norway rats 7 days prior to PDT. Commencing 1 day after CNV induction, 0.5 mL of NAC was orally administered daily to the NAC + group (12 rats), and 0.5 mL of normal saline to the NAC– group (12 rats). Diode laser treatment was delivered for 42 s (total energy, 25 J/cm2) to the left eye prior to verteporfin infusion (PDT–) and to the right eye 15–20 min after such infusion (PDT+). Fluorescein angiography was performed just prior to PDT and enucleation to evaluate fluorescein leakage and CNV closure. We compared the CNV thickness, PDT-induced apoptosis [evaluated via terminal dUTP nick-end labeling (TUNEL)], fluorescein angiographic data, and extents of immunohistofluorescent staining for cleaved caspase-3 and superoxide dismutase (SOD) between the two groups. Results Fourteen days after diode laser treatment, the CNV closure rate was significantly higher in the PDT-treated than the control group. However, the CNV closure rates did not differ significantly between the NAC– and NAC + groups. The TUNEL activity (a measure of PDT-induced apoptosis) of retinal cells was higher in the NAC–/PDT + than the NAC+/PDT + group at 1, 3, 7, and 14 days. The cleaved caspase-3 and SOD levels were higher in the NAC–/PDT + than the NAC+/PDT + group at 3 and 7 days. Conclusions PDT triggers oxygen radical-induced injury to, and apoptosis in, the retina. NAC may reduce PDT-induced damage to the retina without compromising the therapeutic efficacy of CNV. [ABSTRACT FROM AUTHOR]

Photodynamic therapy (PDT) is an office-based treatment for precancerous and early cancerous skin changes. PDT induces cell death through the production of reactive oxygen species (ROS). Cyclobutane pyrimidine dimers (CPDs) are the most important DNA changes responsible for ultraviolet (UV) carcinogenesis. Recently ROS induced by UVA were shown to generate CPDs via activating melanin. This raised the possibility that PDT induced ROS may also induce CPDs and mutagenesis in melanin containing cells. Previously the effect of PDT on CPDs in melanin containing cells has not been assessed. Our current work aimed to compare the generation of CPDs in melanin containing cells subjected to UVA treatment and porfimer sodium red light PDT. We used ELISA to detect CPDs. After UVA we found a dose dependent increase in CPDs in melanoma cells (B16-F10, MNT-1) with CPD levels peaking hours after discontinuation of UVA treatment. This indicated the generation of UVA induced dark-CPDs in the model. Nevertheless, PDT in biologically relevant doses was unable to induce CPDs. Our work provides evidence for the lack of CPD generation by PDT in melanin containing cells. [ABSTRACT FROM AUTHOR]

Prostate cancer (PCa) is the third leading cause of death in men in the United States and its treatment options include surgery, anti-hormonal drugs for androgen sensitive tumors, and radiotherapy. An alternative treatment is the use of photodynamic therapy (PDT), which involves the activation of a photosensitizer by a defined wavelength of light in the presence of oxygen, generating transient concentrations of reactive oxygen species (ROS). In this study, we explored the anti-cancer potential and mechanism of action of PDT using pheophorbide (Pheo) as a photosensitizer in combination with 670 nm LEDs. Our hypothesis was that Pheo-PDT combination will demonstrate anti-cancer activity against androgen dependent PCa (ADPC), suggesting an alternative and less toxic cancer treatment. Pheo-PDT demonstrated significant anti-cancer activity against ADPC in as little as 5 J/cm 2 with increased effects, in a Pheo concentration dependent manner. We also observed in vitro inhibition in the clonogenic potential, as well as significant inhibition of invasion and migration, implicating the anti-metastatic activity of Pheo-PDT on PCa. Furthermore, Pheo-PDT caused G 0 /G 1 cell cycle arrest. The oncolytic activity of PDT involves the generation of ROS, and we demonstrated immediate ROS formation subsequent to Pheo-PDT as well. Mechanistic analysis suggested that the anti-cancer activity of Pheo-PDT is via ER stress, along with inhibition of important cell growth and proliferation markers. Hence, we conclude that Pheo-PDT proves to be a potential therapeutic strategy against ADPC. [ABSTRACT FROM AUTHOR]

Objectives The purpose of this study was to investigate the effects of 5-aminolaevulinic acid mediated photodynamic therapy (ALA-PDT) on the survival activity and apoptosis of human melanoma cell line A375 and non-melanoma skin carcinoma cell line A431 cells. The mechanism for cellular apoptosis was explored. Methods The cell survival activity was determined by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and the proportion of apoptotic cells was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The expression levels of Bcl-2, Bax, caspase-3, caspase-8 and caspase-9 protein were assessed by western blot. The subcellular localization of cytochrome c was comparatively investigated by immunohistochemistry between pre-ALA-PDT and post- ALA-PDT. Results ALA-PDT significantly inhibited the survival activity of A375 cells and A431 cells in a dose- and time-dependent manner. The optimum inhibition efficiencies for A375 cells and A431 cells were obtained at 0.6 mM ALA at 4 h and 8 h after ALA-PDT, respectively. The phenomena of apoptosis were observed in ALA-PDT treated cells by TUNEL assay. The apoptotic rates of A375 cells and A431 cells were 90.0% and 61.5% at 6 h after ALA-PDT, respectively. Apoptosis induced by ALA-PDT involved in down-regulation of Bcl-2 protein, up-regulation of Bax protein and cleaved-PARP protein. It was observed that the expression of cleaved- caspase-3, caspase-8 and caspase-9 proteins in A375 cells and A431 cells gradually increased in 2 h and 4 h but decreased at 4–6 h and 6–8 h after ALA-PDT, respectively. In apoptosis cells immunohistochemical localization show that cytochrome C diffused from the mitochondria into the cytosol. Conclusion ALA-PDT could significantly inhibit the survival activity of A375 and A431 cells. The apoptosis induced by ALA-PDT in A375 and A431 cells was related to the caspase-dependent death-receptor pathway and Cytochrome c-dependent mitochondrial pathway. [ABSTRACT FROM AUTHOR]

Objective To assess the effect of photodynamic therapy (PDT) with talaporfin sodium, a second-generation photosensitizer, on oral squamous cell carcinoma (SCC). Methods Eight patients who were diagnosed with oral SCC without any metastasis and underwent talaporfin sodium-mediated PDT (t-PDT) were included in this study. Biopsies were performed 4–6 weeks after t-PDT. The clinical response was evaluated using Response Evaluation Criteria in Solid Tumors. Results Complete response (CR) was achieved in six of eight cases, and two cases showed partial response (PR) as a clinical outcome of t-PDT. Recurrence occurred in one of the CR cases 9 months after irradiation. The patient underwent tumor resection and no recurrence was found after surgery. The two cases with PR died from the cancer despite additional PDT. Conclusion t-PDT is an effective treatment strategy for oral SCC. Talaporfin sodium has an advantage with regard to early elimination from the body compared with porfimer sodium. [ABSTRACT FROM AUTHOR]

Background The development of nanocarriers is an important approach to increase the bioavailability of hydrophilic drugs in target cells. In this work, we evaluated the anti-tumorigenic mechanisms and efficacy of NanoALA, a novel nanoformulation of aminolevulic acid (ALA) based on poly(lactide- co -glycolide) (PLGA) nanocapsules designed for anticancer photodynamic therapy (PDT). Methods For this purpose, physicochemical characterization, prodrug incorporation kinetics, biocompatibility and photocytotoxicity tests, analysis of the cell death type and mitochondrial function, measurement of the intracellular reactive oxygen species production and DNA fragmentation were performed in murine mammary carcinoma (4T1) cells. Results NanoALA formulation, stable over a period of 90 days following synthesis, presented hydrodynamic diameter of 220 ± 8.7 nm, zeta potential of −30.6 mV and low value of polydispersity index (0.28). The biological assays indicated that the nanostructured product promotes greater ALA uptake by 4T1 cells and consequently more cytotoxicity in the PDT process. For the first time in the scientific literature, there is a therapeutic efficacy report of approximately 80%, after only 1 h of incubation with 100 μg mL −1 prodrug (0.6 mM ALA equivalent). The mitochondria are probably the initial target of treatment, culminating in energy metabolism disorders and cell death by apoptosis. Conclusions NanoALA emerges as a promising strategy for anticancer PDT. Besides being effective against a highly aggressive tumor cell line, the treatment may be economically advantageous because it allows a reduction in the dose and frequency of application compared to free ALA. [ABSTRACT FROM AUTHOR]

• The present work demonstrates the original innovations with the following details: 1). MYBL2 (B-Myb) absence in colorectal cancer contributes to photodynamic therapy (PDT) resistance. 2). MYBL2 deletion in colorectal cancer could activate NF-κB to up-regulate ABCG2 and thus efflux photosensitizers, leading to reduced efficacy of Ce6-PDT thereupon. Photodynamic therapy (PDT) may be an effective therapeutic strategy for colorectal cancer at an early stage. However, malignant cells' resistance to photodynamic agents can lead to treatment failure. MYBL2 (B-Myb) is an oncogene in colorectal carcinogenesis and development, for which little research has focused on its effect on drug resistance. In the present work, a colorectal cancer cell line with a stable knockdown of MYBL2 (ShB-Myb) was constructed first. Chlorin e6 (Ce6) was utilized to induced PDT. The anti-cancer efficacy was measured by CCK-8, PI staining, and Western blots. The drug uptake of Ce6 was assayed by flow cytometry and confocal microscopy. The ROS generation was detected by the CellROX probe. DDSB and DNA damage were assayed through comet experiment and Western blots. The over-expression of MYBL2 was conducted by MYBL2 plasmid. The findings indicated that the viability of ShB-Myb treated with Ce6-PDT was not decreased compared to control SW480 cells (ShNC), which were resistant to PDT. Further investigation revealed reduced photosensitizer enrichment and mitigated oxidative DNA damage in colorectal cancer cells with depressed MYBL2. It turned out that SW480 cells knocking down MYBL2 showed phosphorylation of NF-κB and led to up-regulation of ABCG2 expression thereupon. When MYBL2 was replenished back in MYBL2-deficient colorectal cancer cells, phosphorylation of NF-κB was blocked and ABCG2 expression up-regulation was suppressed. Additionally, replenishment of MYBL2 also increased the enrichment of Ce6 and the efficacy of PDT. In summary, MYBL2 absence in colorectal cancer contributes to drug resistance by activating NF-κB to up-regulate ABCG2 and thereby leading to photosensitizer Ce6 efflux. This study provides a novel theoretical basis and strategy for how to effectively improve the anti-tumor efficacy of PDT. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Glioblastoma multiforme (GBM) is a tumor characterized by rapid cell proliferation and migration. GBM constitutes the most aggressive and deadly type of brain tumor and is classified into several subtypes that show high resistance to conventional therapies. There are currently no curative treatments for malignant glioma despite the numerous advances in surgical techniques, radiotherapy, and chemotherapy. Therefore, alternative approaches are required to improve GBM treatment. Methods Our study proposes the use of photodynamic therapy (PDT) for GBM treatment, which uses chloro-aluminum phthalocyanine (AlClPc) encapsulated in a new drug delivery system (DDS) and designed as a nanoemulsion (AlClPc/NE). The optimal dark non-cytotoxic AlClPc/NE concentration for the U87 MG glioma cell model and the most suitable laser light intensity for irradiation were determined. Experimental U87 MG cancer cells were analyzed via MTT cell viability assay. Cellular localization of AlClPc, morphological changes, and cell death via the necrotic and apoptotic pathways were also evaluated. Results AlClPc remained in the cytoplasmic region at 24 h after administration. Additionally, treatment with 1.0 μmol/L AlClPc under light irradiation at doses lower than 140 mJ/cm resulted in morphological changes with 50 ± 6% cell death (p < 0.05). Moreover, 20 ± 2% of U87 MG cells underwent cell death via the necrotic pathway. Measurement of Caspase-9 and -3 activities also suggested that cells underwent apoptosis. Taken together, these results indicate that AlClPc/NE-PDT can be used in the treatment of glioblastoma by inducing necrotic and apoptotic cell death. Conclusions Our findings suggest that AlClPc/NE-PDT induces cell death in U87 MG cells in a dose-dependent manner and could thus serve as an effective adjuvant treatment for malignant glioma. AlClPc/NE-PDT utilizes a low dose of visible light and can be used in combination with other classic GBM treatment approaches, such as a combination of chemotherapy and surgery. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) and photothermal therapy (PTT) are two known optical remedies of cancer. PTT can be combined with other therapies. One of the limitations of optical therapies is the penetration of light into biological tissues, which reduces its effectiveness due to usage of photosensitizers and PTT agents, which are absorbed in the NIR region that provides the maximum penetration. For instance, Indocyanine green (ICG) serves as a photosensitizer and Gold nanostructures as agents for PTT. GGS is a gold nanoshell with two absorption peaks in the NIR and visible regions. The aim of this study is to evaluate the synergistic effect of PDT and PTT in the presence of GGS conjugated with ICG. Methods After synthesizing GGS, ICG was conjugated with GGS. The specifications and cytotoxicity of agents were identified. Cells were irradiated by an 808 nm laser with or without the agents and three laser outputs were achieved, with each having four different exposure times. The viability of treated cells was determined via MTT assay. Result The irradiation of the laser did not produce any significant effect by itself or in the presence of GGS. The maximum cell death recorded for GGS, ICG and GGS-ICG were 15 ± 7%, 50 ± 3% and 31 ± 3% respectively. ICG and GGS-ICG differs significantly for exposures higher than 2250 J/cm 2 . Conclusion The conjugate was provided through a simple process and a greater chemical stability compared to GGS was achieved. Moreover, it induced a stronger photodynamic and photothermal effect on the cells. This is a promising result which can help enhance the effectiveness of a minimally invasive treatment. [ABSTRACT FROM AUTHOR]

The primary goal of nursing care in cases of endoscopic photodynamic therapy (PDT) for digestive tract carcinoma is to prevent phototoxicity by the intravenous administration of photosensitizers. The adequate protocol and management of patients should be conducted under the instruction of expert physicians. Our experiences of administering porfimer sodium and talaporfin sodium during clinical PDT provide insight regarding the specific management protocol of each photosensitizer during an in-hospital stay. We herein report our nursing protocol based on 15 years of experience. Under adequate management, PDT can be safely performed. [ABSTRACT FROM AUTHOR]

• PDT for oral squamous cell carcinoma and epithelium dysplasia provides reliable short-term outcomes, but its long-term effects are limited. • When PDT is applied to oral squamous cell carcinoma, long-term follow-up is essential because of the high risk of recurrence. • New therapies will need to be developed to acquire the reliable outcome in the future. Oral squamous cell carcinoma (OSCC) treatment consists mainly of surgery, chemotherapy, and radiotherapy, alone or in combination. Epithelial dysplasia (ED) is also treated with surgery. However, these treatments can induce functional and/or aesthetic disturbances. Photodynamic therapy (PDT) can preserve organs. Although short-term studies have shown good progress, long-term evaluations have not yet been conducted. This study aimed to clarify the long-term effects of PDT on OSCC and ED. Methods: Patients who underwent PDT with the first (porfimer sodium) or second generation photosensitizers (talaporfin sodium) for early OSCC (T1 and T2) and ED were included in this study. The long-term prognosis was assessed. Twenty-three patients were included. Complete response (CR) was observed in 19 patients (82.6%) and partial response (PR) in 4 patients (17.4%) 4 weeks after PDT. Regarding long-term progress, local region recurrence occurred in 11 of 19 CR cases (57.9%), and the term of recurrence was 27.4 ± 30.4 months. Surgical resection was performed in all local recurrence and PR cases, and 3 patients died of the underlying disease. PDT provides a good outcome in the short term, but its long-term effects are limited. [ABSTRACT FROM AUTHOR]

• This method is an effective and safe surgical alternative to treatment of Bowen's disease. • This method can increase the penetration depth of photodynamic therapy (PDT). • The treatment regimen has better efficacy and lower recurrence rate than PDT. Bowen Disease (BD), also known as squamous cell carcinoma in situ , requires treatment to prevent progression to invasive cancer.. Photodynamic therapy (PDT) has been widely employed to treat BD. However, there are BD patients who undergo PDT but experience poor efficacy and recurrence. We have considered that for some, the reason is the depth of PDT penetrating tissue to be limited. Therefore, we combined simple shaving with PDT to treat 10 patients with a total of 44 advanced BD lesions. After local injection of anesthesia, the lesions were shaved once in situ , then a total of three PDT sessions were applied for each patient. At 12 weeks, all of BD lesions (100%) have shown complete clinical response. After more than 12 months follow-up, the RR was 0, and all lesions showed a good or excellent cosmetic outcome. The patient's symptoms were alleviated with improvement in the quality of life. For those with advanced BD, which are more than 3 cm in diameter, with unclear borders, ulcers, multiple occurrences and those that appear on the face and neck that are not suitable for extended resection by routine surgery, combined simple shaving with PDT is recommended. [ABSTRACT FROM AUTHOR]

Highlights • PDT has a good effect in treating vulval CA in pregnancy. • The recurrence rate of CA in pregnancy is low after treatment with PDT. • PDT can be used to treat vulval CA in pregnancy. Abstract Objective To observe the clinical efficacy of 5-aminolevulinic acid photodynamic therapy (ALA-PDT) in treating vulval condylomata acuminata (CA) in pregnancy. Methods The clinical efficacies of ALA-PDT on 16 cases of CA in pregnancy as well as cryotherapy on 22 cases of CA in pregnancy were analyzed in this prospective study. Results The treatment group showed a wart clearance rate of 93.8% after 3 PDT treatments, while the control group showed a wart clearance rate of 72.7% after 3 cryotherapy treatments. After the 3-month follow-up period, the treatment group registered a recurrence rate of 6.3%, whereas the control group recorded a recurrence rate of 36.4%, indicating a statistically significant difference (χ2 = 4.674, p = 0.031 < 0.05). After the 1-month postpartum follow-up period, the newborns grew and developed well, without any abnormality in physical examinations. Conclusion ALA-PDT is safe and effective in treating CA in pregnancy. [ABSTRACT FROM AUTHOR]

Previous studies suggest that apoptosis of carcinoma cells led by photodynamics is mainly intrinsic apoptosis, but whether the extrinsic pathway is involved in the treatment of carcinoma by photodynamic therapy is not confirmed. This research investigated the effect of ALA-PDT on the proliferation and apoptosis of SCC cell A431 and COLO-16, and discussed the role played by JAK/STAT3 signal pathway in this process. Our data showed that the expression levels STAT3 and p-STAT3 protein in the cancer tissue are higher than the corresponding adjacent tissue to carcinoma. The expression level of p-STAT3 in cancerous tissue has a correlation with the tumor size and tissue histopathological differentiation. ALA-PDT could inhibit proliferation of A431 and COLO-16 cells, STAT3 knock down could enhance ALA-PDT's inhibition of cell proliferation, and promote apoptosis induced by ALA-PDT. On the other hand, overexpression of STAT3 has the opposite effect. In addition, ALA-PDT can weaken the protein expression of STAT3 and its target gene Bcl-2 mRNA, and ALA-PDT can strengthen the protein expression of STAT3's target gene Bax mRNA. Overexpression of STAT3 can offset the effect on Bcl-2 and Bax by ALA-PDT; on the other hand, STAT3 knocking down can strengthen ALA-PDT's effect on Bcl-2 and Bax. [ABSTRACT FROM AUTHOR]

Objectives Photodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up. Materials and methods Thirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2 mg/kg) intravenously 48 h prior to light irradiation. Photoradiation was performed at doses of 100–150 J/cm 2 using a 630-nm wavelength excimer dye laser. Results Six months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed. Conclusion PDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects. [ABSTRACT FROM AUTHOR]

Attachment of Protoporphyrin IX (PPIX) to poly (styrene- co -4-vinylpyridine) (PS4VP) nanobeads was carried out to improve its properties in aqueous solutions. After using an oil-in-water heated emulsion polymerization technique to synthesize PS4VP, PPIX was bonded to the particles via the carboxylic acid of PPIX hydrogen-bonding to the nitrogen at the surface of PS4VP, thereby preventing self-reactions between the carboxyl groups and the porphyrin core. Refraining the two parts from interacting while attached to the nanobeads prevented PPIX from aggregating, which then increased water solubility, enhanced luminescence and singlet oxygen production. Attachment also improved cell uptake and cell destruction by photodynamic activity. This shows that PS4VP-PPIX may help improve aspects of photodynamic therapy for the treatment of cancer. [ABSTRACT FROM AUTHOR]

5-Aminolaevulinic acid-based photodynamic therapy (ALA-PDT) has been used for part of squamous cell carcinoma (premalignant conditions or in situ cutaneous SCC–Bowen disease). However, mechanism of ALA-PDT is not fully understood yet on the cell apoptosis pathway. The aim of this study was to further investigate the effect and mechanism of 5-ALA-PDT on human squamous carcinoma A431cells. Apoptosis and cell viability after PDT were evaluated using Annexin V-FITC apoptosis detection kit and MTT assay. The mRNA and protein levels were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Our data showed that 5-ALA-PDT significantly inhibited cell proliferation ( p < 0.05), but there was no significant difference when the photosensitizer reached to 4.8 mM. The inhibition in cell proliferation after 5-ALA-PDT treatment was correlated to more cells being arrested in the G0/G1 phase of the cell cycle ( p < 0.01). Immunocytochemical observations using anti-active caspase-3 antibodies showed active caspase-3 was translocated from cytoplasm to nuclear during apoptosis. STAT3 and its downstream gene Bax and BCL-2 were changed after 5-ALA-PDT treatment for the mRNA and protein expression. Our studies confirmed that 5-ALA-PDT might be an effective treatment for human squamous carcinoma by inhibiting the tumor cell A431growth and for the first time demonstrated that the expression of STAT3 was significantly reduced at 24 h after 5-ALA-PDT treatment. [ABSTRACT FROM AUTHOR]

Objective Our aim was to study photodecomposition, photomutagenicity and cytotoxicity of retinyl palmitate (RP), a principal storage form of vitamin A in humans and animals, under He–Ne laser photoirradiation. Moreover, the effect of different concentrations and timing protocol of antioxidants on photodynamic therapy (PDT) is contradictory, so the effect of RP (as antioxidant) on the PDT cytotoxicity was studied. Methods Photomutagenicity was tested by Ames test. Photodecomposition was studied by UV–vis spectroscopy. Cytotoxicity was measured with MTT-assay. Moreover, the effect of PDT, using hematoporphyrin derivatives (HpD) as photosensitizer under He–Ne laser irradiation (10 J/cm 2 ), was studied on HeLa cells either with or without RP (1–100 μM) which incubated with the cells for short or long incubation period (1 h or 24 h) prior to PDT. Results No photodecomposition of RP alone was obseved whereas there is a little photodecomposition of RP only in presence of HpD under irradiation with He–Ne laser. Moreover, no photomutagenicity was observed in Salmonella typhimurium strains under laser irradiation in presence or absence of HpD. RP alone (1–100 μM) significantly decrease the viability of HeLa cells. Laser irradiation of HeLa cells pre-incubated with RP alone for 24 h showed further significant decrease in viability of the cells. While RP incubations for 1 h before PDT had slight effect on the cells, 24 h incubation before PDT enhanced the cytotoxicity of PDT on HeLa cells. Conclusions RP can be used 24 h before PDT to enhance its effects. RP is not mutagenic under irradiation with He–Ne laser. [ABSTRACT FROM AUTHOR]

Background data Methylene blue (MB) and toluidine blue (TB) are recognized as safe photosensitizers (Ps) for use in humans. The clinical effectiveness of the antimicrobial photodynamic therapy with MB and TB needs to be optimized, and ethanol can increase their antimicrobial effect. Formulations of MB and TB containing ethanol were evaluated for their ability to produce singlet oxygen and their antibacterial effect on Pseudomonas aeruginosa biofilms. Methods Photoactivated formulations were prepared by diluting the Ps (250 μM) in buffered water (pH 5.6, sodium acetate/acetic acid), 10% ethanol (buffer: ethanol, 90:10), or 20% ethanol (buffer: ethanol, 80:20). Biofilms also were exposed to the buffer, 10% ethanol, or 20% ethanol without photoactivation. Untreated biofilm was considered the control group. The production of singlet oxygen in the formulations was measured based on the photo-oxidation of 1,3-diphenylisobenzofuran. The photo-oxidation and CFU (log 10 ) data were evaluated by two-way ANOVA and post-hoc Tukey’s tests. Results In all the formulations, compared to TB, MB showed higher production of singlet oxygen. In the absence of photoactivation, neither the buffer nor the 10% ethanol solution showed any antimicrobial effect, while the 20% ethanol solution significantly reduced bacterial viability ( P = 0.009). With photoactivation, only the formulations containing MB and both 10% and 20% ethanol solutions significantly reduced the viability of P. aeruginosa biofilms when compared with the control. Conclusions MB formulations containing ethanol enhanced the antimicrobial effect of the photodynamic therapy against P. aeruginosa biofilms in vitro. [ABSTRACT FROM AUTHOR]

• Evaluated the photodynamic therapy (PDT) of liposomally formulated indocyanine green derivative (ICG-Lipo) that encapsulated carboplatin and docetaxel (ICG-Lipo-C&D). • Chemotherapeutic PDT (chemo-PDT) nanoscale drug delivery system using ICG-Lipo-C&D was evaluated. • Chemo-PDT using ICG-Lipo possesses potential as a promising cancer therapy. Photodynamic therapy (PDT) utilizes the enhanced permeability retention effect of photosensitizers and is less invasive and more selective than traditional chemotherapy. We constructed a chemotherapeutic PDT (chemo-PDT) nanoscale drug delivery system using a liposomally formulated indocyanine green derivative (ICG-Lipo) that encapsulated carboplatin and docetaxel (ICG-Lipo-C&D). The antitumor effect of chemo-PDT mediated by ICG-Lipo-C&D was evaluated in a murine colon 26 CDF1 mouse model. Gene expression in tumor tissues was analyzed by RNA sequencing. Chemo-PDT using ICG-Lipo-C&D demonstrated an even stronger PDT-enhancing effect than did ICG-Lipo due to the synergistic effect of carboplatin and docetaxel. In addition, gene expression analysis showed that PDT with ICG-Lipo-C&D increased the expression of immune-related genes and decreased the expression of cytoskeleton-related genes. Chemo-PDT using ICG-Lipo as a photosensitizer as well as a drug delivery system with an enhanced permeability retention effect may be a promising cancer therapy. [ABSTRACT FROM AUTHOR]

Summary Molecular modification of protoporphyrin IX (PpIX) was conducted to improve its water solubility and therapeutic performance for photodynamic therapy. The carboxylic acid and the two nitrogen atoms in the core of PpIX molecule were protonated following by conjugation with 3-aminopropyl triethoxysilane (APTES). Then, folic acid (FA) was conjugated to the APTES-coated PpIX (MPpIX) through chemical bonding between FA and protonated PpIX. The results showed that APTES coating can stabilize PpIX and increase its water solubility. Consequently, this leads to the enhancement in luminescence and singlet oxygen production. Upon X-ray irradiation, singlet oxygen can be detected in the MPpIX but not in PpIX. This means that MPpIX can be used for deep cancer treatment as X-ray can penetrate deeply into tissue. Molecular modification also reduces the dark toxicity of PPIX and increases their cell uptake. All these traits indicate that the Molecular modification of PpIX may potentially improve the efficacy of photodynamic therapy for cancer treatment. [ABSTRACT FROM AUTHOR]

Background Photodynamic therapy (PDT) is an established cancer treatment. Molecular-targeted agents targeting phosphatidylinositol 3-kinase (PI3K) pathway is showing great promise as anticancer drugs. This study compared SVEC mouse endothelial and PC-3 human prostate tumor cells in the response to verteporfin-mediated photodynamic therapy (PDT) and a pan-PI3K pathway inhibitor LY294002. Methods Verteporfin cellular uptake and intracellular localization was determined by spectrofluorometry and confocal fluorescence microscopy, respectively, in the SVEC and PC-3 cells. Cytotoxicity induced by LY294002 and verteporfin-PDT was assessed by the MTS assay. Effects of treatments on cell survival and death signaling were examined by Western blot analysis. Results PC-3 cells had a higher cellular uptake of verteporfin than SVEC cells at 15 min after incubation with verteporfin. Verteporfin was mainly localized in mitochondria in both SVEC and PC-3 cells. Verteporfin-PDT alone as well as PDT in combination with LY294002 induced more apoptosis and caused more reduction in cell viability in SVEC cells than in PC-3 cells. PC-3 cells exhibited a higher level of anti-apoptotic Bcl-2 family proteins than SVEC cells. Conclusions SVEC cells were more responsive to verteporfin-PDT and PI3K pathway inhibitor LY294002 than PC-3 cells. Such differences in response were likely due to differences in Bcl-2 family protein level. These results support tumor vascular targeting by verteporfin-PDT and its therapeutic enhancement by PI3K pathway inhibition. [ABSTRACT FROM AUTHOR]

Summary: Background: The goal of the current research is to evaluate the potential of photodynamic therapy (PDT) in the treatment of triple negative breast cancer (TNBC) with the development of a theranostic thermosensitive liposome platform to deliver indocyanine green (ICG) as the near-infrared (NIR) photosensitizer excited by an 808nm diode laser. Methods: In the PDT protocol, an optimized thermosensitive liposome formulation is investigated to formulate ICG as the photosensitizer, which is exited by laser light at the wavelength of 808nm delivered by a fiber-coupled laser system. ICG in both free solution and thermosensitive liposomal formulation were evaluated as the NIR photosensitizer and compared in the PDT treatment on a panel of triple negative breast cancer cell lines along with the nontumorigenic mammary epithelial cell line MCF-10A. In addition to cytotoxicity, and clonogenic survival assessment, the role of DNA double strand break damage was evaluated. Results: Both MTT and clonogenic assays revealed that PDT using ICG inhibited the growth of several TNBC cell lines as well as the non-tumorigenic human breast epithelial cell line MCF-10A; and the liposomal formulation of ICG did not compromise the in vitro treatment potency, though free ICG performed slightly more effective in certain cell lines, but was not statistically significant. Cell viability was dose dependent in regards to ICG concentration and irradiation energy. Interestingly, PDT using the described protocol was more potent to inhibit the growth of MDA-MB-468 and HCC-1806 cells, coinciding with the observation that these cells are more sensitive toward DNA damaging agents. In comparison, cell lines HCC-70, BT-549, and MCF-10A were found to have less of an inhibitory effect. Furthermore, substantial DNA double strand breaks (DSBs) were observed 30min after the PDT treatment via a γ-H2AX staining assay. PDT induced DNA damage has the potential to lead to mutagenicity, which may have various responses depending on the repair capabilities of the cells. Conclusion: Our results suggest that PDT using indocyanine green loaded liposomes were effective in inhibiting tumor cell growth to varying extents with higher responses observed for MDA-MB-468 and HCC-1806 cells. [Copyright &y& Elsevier]

Summary: Background: Light fractionation with a 2-h dark interval increases the efficacy of topical aminolevulinic acid (ALA) photodynamic therapy (PDT). Hexyl-aminolevulinate (HAL) is the hexyl ester of ALA. Both HAL and ALA lead to protoporphyrin IX (PpIX) accumulation in endothelial cells and to vascular effects, which are important for light fractionation. We investigated light fractionation for HAL-PDT in a mouse skin model and compared this with ALA. Methods: Three illumination schemes were studied: (a) 100Jcm−2 in a single illumination; (b) 50+50Jcm−2 in a twofold illumination; (c) a small first light fraction until 50% of PpIX was photobleached (ca. 3Jcm−2), followed by 97Jcm−2 2h later. PpIX fluorescence was measured continuously during illumination. Efficacy was evaluated by daily visual skin damage scoring up to 7 days after PDT. Results: Light fractionation showed a trend towards increased efficacy for HAL-PDT. Both the initial PpIX synthesis and the PpIX resynthesis during the dark interval were higher for ALA, but these were not correlated with efficacy. Single HAL-PDT was more effective than single ALA-PDT. Photobleaching rates of HAL and ALA were similar indicating similar biodistributions at depth. Conclusion: Our results provide evidence to support that light fractionation may be beneficial for HAL-PDT. We are cautious because we found only a non-significant increase in response. However, combining our results with literature data suggest that the illumination scheme may be further optimized for HAL-PDT to potentially enhance the effect of light fractionation. [Copyright &y& Elsevier]

Summary: Background: Photodynamic therapy (PDT) with precursors of photoactivable porphyrins is a well-established treatment modality for skin pathologies as well as hair removal. Pain is a major side effect thereof, and it affects the treatment compliance and acceptance. Methods: Five male subjects underwent a PDT procedure on normal skin, either with a diode laser (635nm) or a lamp (405nm), 3 or 6h after application of various precursors of photoactivable porphyrins (ALA 1M; Metvix® 1M; ALA-DGME 1M; ALA-DGME 3.66M). Light doses ranged from 30 to 150J/cm2 and irradiances were 100 or 180mW/cm2. Fluorescence measurements were performed just before PDT, pain was quantified during PDT, and erythema was determined 24h afterwards. Results: Because precursor ALA-DGME was very selective for the pilosebaceous apparatus vs. the epidermis, we solely carried out the PDTs using this precursor. In the absence of light, no pain was reported. An increase in pain was observed when increasing the irradiance. A correlation was observed between the follicular fluorescence and the maximal pain score during PDT. A correlation was observed between follicular fluorescence and skin erythema, and between pain score and skin erythema. Conclusions: With our well-controlled PDT parameters and homogenous subjects’ conditions, we showed that pain could be reduced by reducing irradiance during PDT procedures. With the various correlations observed, we conclude that both pain and PaP fluorescence are useful tools to predict the post-PDT tissue effects (side effects and outcome). We suggest that A∂ nerve fibres would be the best candidate as first generators of PDT-induced pain. [Copyright &y& Elsevier]

Summary: Background: Anal Intraepithelial Neoplasia (AIN), a pre-cursor of anal squamous carcinoma, is increasingly detected in individuals with impaired immune function. However, choices for effective, low morbidity treatment are limited. Photodynamic Therapy (PDT) is promising as it is known to ablate more proximal gastrointestinal mucosa with safe healing, without damage to underlying muscle. It can also ablate skin with safe healing and minimal scarring. Methods: Pharmacokinetics: Normal rats were sensitised with 200mg/kg 5-aminolaevulinic acid (ALA) and killed 1–8h later. Anal tissues were examined by fluorescence microscopy to quantify the concentration of PPIX (protoporphyrin IX, the active derivative of ALA) in anal mucosa and in the underlying sphincter. PDT: Normal rats were sensitised similarly 3h later, laser light (635nm) was delivered. Anal canal: 50–150J/cm using 1cm diffuser fibre; for peri-anal skin, 50–200J/cm2, using microlens fibre. In each group, 2 rats were killed 3, 7, 14 and 28days later and the anal region removed for histological examination. Results: Pharmacokinetics: Peak concentration of PPIX in mucosa was at 3h, peak ratio mucosa: muscle, 6, seen at same time. PDT. Anal canal 50J/cm: complete mucosal ablation by 3 days, complete regeneration by 28 days. Higher energies caused muscle damage with scarring. Peri-anal skin: 200J/cm2; complete ablation of skin, including appendages, complete healing by 28 days. Minimal effect with lower energy. Conclusion: ALA-PDT can ablate anal mucosa and peri-anal skin with safe healing and no underlying damage. However, over treatment can damage the sphincters. This technique is ready to undergo clinical trials. [Copyright &y& Elsevier]

Summary: Background: 5-Aminolevulinic acid (ALA) or its esters mediated photodynamic therapy (PDT) is the most widely practiced form of PDT in dermatology. One of its advantages is that undesirable photosensitization lasts only for 24–48h. In order to optimize ALA–PDT it is necessary to understand the mechanisms of intracellular production and clearance of PpIX (efflux from cells into blood stream and/or its conversion into haem). The aim of this study is to investigate the factors controlling the clearance of intracellular PpIX from healthy skin of mice. Methods: PpIX was induced in mouse skin by topical or systemic application of ALA or by topical application of the iron chelator ethylenediaminetetraacetic acid (EDTA). Fluorescence spectroscopy was used to study PpIX kinetics in alive and dead skin. Results: Topical application of ALA or EDTA leads to porphyrin production in living skin, but not in excised skin. The clearance rates of PpIX from alive and dead skin were the same in the absence of an intracellular ALA pool. The clearance half-life of EDTA-induced PpIX was 4–7 times longer than that of PpIX after application of ALA. Conclusions: Skin temperature and intracellular iron availability strongly affect PpIX clearance, while ALA application mode (topical versus systemic) and skin viability (dead versus alive) have no influence on PpIX decay. These results demonstrate that the clearance kinetics of PpIX from skin are determined mostly by the conversion of PpIX into haem, while the cellular efflux of PpIX into blood plays a minor role. [Copyright &y& Elsevier]

Summary: Background: The aim of this study was to clarify the mechanism of accumulation of 5-aminolevulinic acid (ALA)-dependent protoporphyrin IX (PpIX), ALA-photodynamic therapy (PDT)-induced cell death and enhanced efficiency by a ferrochelatase inhibitor in prostate cancer PC-3 cells. Methods: The accumulation of ALA-induced PpIX in PC-3 cells was observed by fluorescence microscopy and measured by flow cytometry analysis. The efficiency of ALA-PDT was analyzed by flow cytometry and assessed by cell death, caspase-3 activity and mitochondrial membrane potential. The ALA-PDT-promoting effects of ferrochelatase inhibitors, such as deferoxamine and NOC-18, were also analyzed. We confirmed the results obtained in vivo with an animal model using nude mice. Results: ALA-induced PpIX accumulation increased in time- and ALA concentration-dependent manners. ALA-PDT decreased the levels of mitochondrial membrane potential, and induced cell death occurred by both apoptosis and necrosis. Inhibition of ferrochelatase by deferoxamine and NOC-18 led to increase of PpIX accumulation and enhanced effect of ALA-PDT in PC-3 cells. In vivo, the degeneration of tumor tissue by ALA-PDT was observed within a broader range and led to apoptosis and necrosis. Conclusion: This study demonstrated ALA-PDT induced PC-3 cell death by the mechanisms of both necrosis and apoptosis through a caspase-independent mitochondrial pathway. Inhibition of ferrochelatase enhanced these effects, suggesting that ferrochelatase played an important role in ALA-PDT. ALA-PDT could be a new modality for focal therapy of prostate cancer. [Copyright &y& Elsevier]

Summary: Background: In this study, the photosensitivity of 5-aminolevulinic acid (5-ALA) conjugated gold nanoparticles (conjugate) has been investigated on the MeL-Rm cell line. Methods: After culture and proliferation of the Mel-Rm cell line, cell toxicity and the suitable cell incubation time of the conjugate were determined. Photosensitivity of the conjugate and free 5-ALA was then studied in optical doses of 20, 40, 60 and 80J/cm2 while light irradiation was applied by a He–Ne laser. Results: A 4-h time interval was determined as the optimum incubation time for 5-ALA and the conjugate. PpIX induction into the cells showed a significant increase after incubation with the conjugate in comparison to 5-ALA alone. Also, the conjugate resulted in a two times higher cell death rate compared to free 5-ALA. Conclusion: The conjugate can be used as an appropriate delivery agent for 5-ALA and provide efficient cell destruction during PDT. [Copyright &y& Elsevier]

Summary: Oral 5 aminolevulinic acid (5-ALA) is used to assist surgical resection of malignant tumours in the brain and other locations. Hypotension and alteration of liver functions have been reported as potential adverse effects. This study was designed to assess the incidence and contributing factors that cause 5-ALA induced side effects in a cohort of 90 patients. Hypotension occurred in 11% of patients irrespective of 5-ALA dose. The only contributing factor was the presence of cardiovascular disease and antihypertensive drug therapy with an odd ratio of 17.7. Liver function were disturbed in 2% in patients who received 20mg or less/kg body weight compared to 4% in those who received a dose of >20mg/kg 5-ALA. The liver dysfunction was minor and was not clinically significant. We concluded that 5-ALA induced side effects were minimal and hypotension more likely to occur in patients receiving antihypertensive drug therapy. [Copyright &y& Elsevier]

Summary: Introduction: MBT carry poor prognosis and more than 80% of MBT recur locally within 2cm of the resection margin because of inadequate surgical removal. A number of techniques have been implemented in recent years to improve surgical removal of MBT with variable success. We examined two methods commonly used to resect MBT to establish which one offered the best chances of gross total removal; MRI guided technology and ALA-induced fluorescence. Patients and methods: Twenty consecutive patients diagnosed with MBT were included in this study. They were given 20mg ALA per kg body weight 3h before anaesthesia orally mixed in water. Surgery was planned using preoperative enhanced MPR age images. Surgery was executed using the Stealth Station image guidance system and ALA-induced fluorescence microsurgical techniques. During surgery the intensity of fluorescence was graded into red, pink or blue. The intensity of fluorescence was also measured using pulsed 405nm laser and a compact spectrometer using a touch probe directly placed on the tissue. The extent of tumour invasion was assessed intraoperatively using standard white light, blue light and spectroscopic measurements. Postoperative enhanced MRI was used to assess the extent of resection and the volume of residual tumour was measured. Results: There were six newly diagnosed GBM, eight recurrent GBM, one oligodendroglioma (ODG) and five metastases (MET). On enhanced MRI, the mean diameter of new GBM, recurrent GBM, ODG and MET was 2.3cm, 2.3cm, 1.5cm, and 2.3cm respectively. Under the blue light, the mean diameter of new GBM, recurrent GBM, ODG and MET was 2.9cm, 3cm, 1.5cm and 2.3cm respectively. The results of quantitative measurements of fluorescence ratios revealed that red fluorescence corresponded to 5.9–11.6 (solid tumour on histology), and pink fluorescence measured 0.8–1.9 (infiltrating edge of tumour on histology). When we compared the maximum tumour diameter of GBM we found on average it was 10mm wider on spectroscopy compared to standard white light microscopy and 6mm wider than what the enhanced MRI demonstrated. Conclusions: Fluorescence technology revealed that GBMs are wider than the enhanced MRI had demonstrated, while MET enhanced MRI was similar in size to fluorescence. Furthermore, solid tumour can be identified intraoperatively and can be measured using fluorescence and spectroscopy techniques and it can be removed safely. Infiltrating tumour can also be identified intraoperatively using this technology and can be removed in non-eloquent areas to maximise surgical resection. [Copyright &y& Elsevier]

• PDT is booming with continuing development of new photosensitizers and medical indications. • Current light devices give only limited choice of treatment area and spectral qualities. • We show a new LED device with an array of different light colours from blue to infrared to spectrally match with the absorption spectra peaks of a wide range of photosensitizers. • The device allows the irradiation field to be close matched to the lesion area. • Preliminary results show the promise of this use easy and low-cost LED device for different PDT modalities. One of the key aspects of photodynamic therapy is the light source that is used to irradiate the lesion to be treated. The devices used must ensure that their emission spectrum matches the absorption spectrum of the photosensitizer, so that treatment radiation is delivered only on the target area, without irradiating healthy tissue at superficial or deep levels. Irradiance values must be adequate in order to avoid thermal damage, exceed the oxygen replenishment rate and avoid long treatment times. Furthermore, the device should be user-friendly, inexpensive, and able to be adapted to different photosensitizers. We have developed an easy-to-use and highly customizable device based on LED technology. Its innovative geometric design allows radiation to be delivered to a small treatment surface, since the LEDs are arranged in three arms, the configuration of which directs their radiation on the treatment point. Different high-power color LEDs are disposed on the arms, and can be independently selected based on the most effective wavelengths for exciting the different photodynamic therapy photosensitizers. We have tested the prototype in 5 different patients (1 actinic keratose, 1 actinic cheilitis, 1 superficial basal cell carcinoma and 2 Bowen's disease) and after 1–2 sessions of total cumulative dose of 25–50 J / cm2, 100% clearance of lesions were obtained. Our device can be used by any professional in the field, whether for medical or research purposes. It facilitates the development of treatment protocols and trials with different photosensitizers. A key aspect of photodynamic therapy is the light source used to radiate the lesion to be treated. We have developed an LED-based array capable of emitting colors from blue to infra-red so that the emission spectrum can be matched to the absorption spectrum of many photosensitizers, with the capacity to focus the light beam on the lesion area, and with LED energy control for irradiance selection. So, healthy tissue can be protected and treatment duration as well as light spectrum can be easily controlled. Preliminary tests in a set of patients and different skin lesions show our device to be a promising easy to use, low cost and easily controllable light source. [Display omitted] [ABSTRACT FROM AUTHOR]

• Ce6 mediated PDT could induce obvious DNA damage and activate ATM-related DNA damage response (DDR) through generation of ROS in a short period time. • ATM inhibitor could ameliorate the efficacy of Ce6-triggered PDT for lung cancer by blocking the DDR. • The present study reveals a novel resistance mechanism of PDT and proposes an intervention strategy by the use of ATM inhibitor. Photodynamic therapy (PDT) is a promising strategy for the treatment of malignant tumors due to its high selectivity, limited-toxicity, and non-invasiveness. However, PDT can also induce DNA damage and subsequent repair response, which may reduce the efficacy of PDT. In the present study, we sought to explore the effect of chlorin e6 (Ce6)-mediated PDT on DNA damage and DNA damage response (DDR) in lung cancer cells. In addition, the effect of PDT combined with ATM inhibitor on molecules of DDR and the possibility of improving the efficacy of PDT were further investigated. In the in vitro study, lewis cells were submitted to Ce6 treatment (2, 4, 8, 16, 32 μg/mL). To determine the concentration of Ce6, uptake and toxicity of Ce6 mediated PDT were detected using flow cytometry (FACS), Confocal microscopy, and CCK-8. In the subsequent research, 8 μg/mL of Ce6 was the treatment condition for inducing PDT. The different post-irradiation placement times were further grouped under this condition (2, 4, 6, 12 h). Cellular reactive oxygen species (ROS), damage of DNA were measured by DCFH-DA probe, comet assay respectively. Then the expression of p-ATM, p53, and γ-H2A.X proteins related to DNA damage response, was detected by WB. The efficacy of Ce6 induced PDT was also demonstrated by Annexin-V/PI staining as well as the expression of PCNA, cleaved-caspase-3. On this basis, ATM inhibitor was applied to treat lewis cells combined with Ce6 (2, 4 h) to investigate whether the efficacy of PDT induced by Ce6 can be improved after the ATM-related DDR was blocked. The cell viability, apoptosis, and expression of associated proteins were assayed. At 2–4 h after PDT treatment, ROS was dramatically elevated in lewis cells, DNA double-strand breaks (DDSB) occurred, as well as up-regulation of DDR proteins γ-H2A.X, p-ATM, and p53. At the same time, lewis cells did not undergo significant apoptosis. After ATM inhibition, the DDR was significantly blocked within 2–4 h after Ce6 induced PDT, along with a pronounced decrease in cell viability followed by a prominent increase of apoptosis. Ce6-mediated PDT generates ROS in a short period time, thus inducing DNA damage, ATM-related DDR as well as promoting resistance of lung cancer cells to PDT. Combining ATM inhibitor with PDT could effectively inhibit the DDR induced by PDT, thereby enhancing the efficacy. This study reveals a new resistance mechanism of PDT and proposes an intervention strategy. [ABSTRACT FROM AUTHOR]

• The behavior of chlorine aluminum phthalocyanine in DNA polymeric film was studied. • The visible light over the DNA-PFs-AlClPc showed a reduction in cell viability. • With low energy fluency DNA-PFs-AlClPc did not show a cytotoxic effect in cancer. • The results have relevance on DNA-PFs-AlClPc as a diagnosis and treatment system. The present study examines the design of DNA polymeric films (DNA-PFs) associated with aluminum chloride phthalocyanine (AlClPc) (DNA-PFs-AlClPc), as a promising drug delivery system (DDS), applicable for breast cancer treatment and early-stage diagnosis using photodynamic therapy (PDT). This study starts evaluating (MCF7) as a model for breast cancer cell behavior associated with DNA-PFs. Analyses of the morphological behaviors, biochemical reaction, and MCF7 cell adhesion profile on DNA-PFs were evaluated. SEM and AFM analysis allowed the morphological characterization of the DNA-PFs. Cell viability and cell cycle kinetics studies indicate highly biocompatible material capable of anchoring MCF7 cells, allowing the attachment and support of cell in the same structure where the insertion of AlClPc (DNA-PFs-AlClPc). The application of visible light photoactivation based on classical PDT protocol over the DNA-PFs-AlClPc showed a reduction in cell viability with increased cell death proportional to the fluency energy range from 600, 900, and 1800 mJ cm−2. The 3D organoid system mimics the tumor microenvironment which was precisely observed in human breast cancer in early-stage progression in the body. The results observed indicate that the viability was reduced by more than 80% in monolayer culture and around 50% in the 3D organoid cell culture at the highest energy fluency (1800 mJ cm−2). With low energy fluency (100 mJ cm−2,), the DNA-PFs-AlClPc did not show a cytotoxic effect on MCF7 cells, enabling the potential for photodiagnosis of early-stage human breast cancer detection in the initial stage of progression. [Display omitted] [ABSTRACT FROM AUTHOR]