Synergic vascular photodynamic activity by methylene blue-curcumin supramolecular assembly.

A supramolecular assembly was obtained by combining methylene blue (MB) with a natural plant extract, curcumin (Curc), in a stoichiometric ratio of 1:4 in aqueous solution (90% PBS + 10% ethanol) at room temperature. The MB-Curc supramolecular assembly was evidenced by absorption and fluorescence spectroscopies, and the stoichiometry and bonding constant were obtained using Cielens model. Its stability and photostability were evaluated by chromatographic analysis and UV-Vis absorption. The MB-Curc avoids the aggregation of both isolated compounds and efficiently produces singlet oxygen (ΦΔ= 0.52 ± 0.03). Its potential for photodynamic antiangiogenic treatments was evaluated through the vascular effect observed in chicken chorioallantoic membrane (CAM) assay. The results showed intense damage in CAM vascular network by MB-Curc after irradiation, which is higher than the effect of isolated compounds, indicating a synergistic vascular effect. This combination can be essential to prevent cancer revascularization after photodynamic application and improve the efficacy of this approach. The characteristics exhibited by MB-Curc make it a potential candidate for use in cancer treatments through photodynamic antiangiogenic therapy.

Nanostructure-Driven Indocyanine Green Dimerization Generates Ultra-Stable Phototheranostics Nanoparticles.

Indocyanine green (ICG) is the only near-infrared (NIR) dye approved for clinical use. Despite its versatility in photonic applications and potential for photothermal therapy, its photobleaching hinders its application. Here we discovered a nanostructure of dimeric ICG (Nano-dICG) generated by using ICG to stabilize nanoemulsions, after which ICG enabled complete dimerization on the nanoemulsion shell, followed by J-aggregation of ICG-dimer, resulting in a narrow, red-shifted (780 nm→894 nm) and intense (≈2-fold) absorbance. Compared to ICG, Nano-dICG demonstrated superior photothermal conversion (2-fold higher), significantly reduced photodegradation (-9.6 % vs. -46.3 %), and undiminished photothermal effect (7 vs. 2 cycles) under repeated irradiations, in addition to excellent colloidal and structural stabilities. Following intravenous injection, Nano-dICG enabled real-time tracking of its delivery to mouse tumors within 24 h by photoacoustic imaging at NIR wavelength (890 nm) distinct from the endogenous signal to guide effective photothermal therapy. The unprecedented finding of nanostructure-driven ICG dimerization leads to an ultra-stable phototheranostic platform.

Photodisinfection of material surfaces and bacterial skin infections by a detergent loaded with curcumin.

The development of technologies and therapeutic strategies is needed to combat skin infections and pathogenic microorganisms present on material surfaces that are still responsible for serious public health problems. In this study, detergents loaded with curcumin were prepared by a simple approach and characterized by UV-vis spectroscopy and fluorescence spectroscopy. Their antibacterial photodynamic effects were evaluated against Staphylococcus aureus in planktonic medium and in vivo (skin infection model), and showed a reduction up to 8 logs and 2 logs, respectively. Additionally, the curcumin-detergents were applied on photodisinfection of material surfaces such as wood, rubber, and stainless steel resulting in an efficient photoinactivation up to 3 logs. These developed detergents loaded with curcumin can improve the decontamination of material surfaces and skin infections (in vivo) when illuminated.

Graphene Oxide Theranostic Effect: Conjugation of Photothermal and Photodynamic Therapies Based on an in vivo Demonstration.

INTRODUCTION: Cancer is the second leading cause of death globally and is responsible, where about 1 in 6 deaths in the world. Therefore, there is a need to develop effective antitumor agents that are targeted only to the specific site of the tumor to improve the efficiency of cancer diagnosis and treatment and, consequently, limit the unwanted systemic side effects currently obtained by the use of chemotherapeutic agents. In this context, due to its unique physical and chemical properties of graphene oxide (GO), it has attracted interest in biomedicine for cancer therapy. METHODS: In this study, we report the in vivo application of nanocomposites based on Graphene Oxide (nc-GO) with surface modified with PEG-folic acid, Rhodamine B and Indocyanine Green. In addition to displaying red fluorescence spectra Rhodamine B as the fluorescent label), in vivo experiments were performed using nc-GO to apply Photodynamic Therapy (PDT) and Photothermal Therapy (PTT) in the treatment of Ehrlich tumors in mice using NIR light (808 nm 1.8 W/cm2). RESULTS: This study based on fluorescence images was performed in the tumor in order to obtain the highest concentration of nc-GO in the tumor as a function of time (time after intraperitoneal injection). The time obtained was used for the efficient treatment of the tumor by PDT/PTT. DISCUSSION: The current study shows an example of successful using nc-GO nanocomposites as a theranostic nanomedicine to perform simultaneously in vivo fluorescence diagnostic as well as combined PDT-PTT effects for cancer treatments.

Carbon-Based Materials in Photodynamic and Photothermal Therapies Applied to Tumor Destruction.

Within phototherapy, a grand challenge in clinical cancer treatments is to develop a simple, cost-effective, and biocompatible approach to treat this disease using ultra-low doses of light. Carbon-based materials (CBM), such as graphene oxide (GO), reduced GO (r-GO), graphene quantum dots (GQDs), and carbon dots (C-DOTs), are rapidly emerging as a new class of therapeutic materials against cancer. This review summarizes the progress made in recent years regarding the applications of CBM in photodynamic (PDT) and photothermal (PTT) therapies for tumor destruction. The current understanding of the performance of modified CBM, hybrids and composites, is also addressed. This approach seeks to achieve an enhanced antitumor action by improving and modulating the properties of CBM to treat various types of cancer. Metal oxides, organic molecules, biopolymers, therapeutic drugs, among others, have been combined with CBM to treat cancer by PDT, PTT, or synergistic therapies.

Photophysics of J-Aggregating Porphyrin-Lipid Photosensitizers in Liposomes: Impact of Lipid Saturation.

Porphyrin aggregates have attractive photophysical properties for phototherapy and optical imaging, including quenched photosensitization, efficient photothermal conversion, and unique absorption spectra. Although hydrophobic porphyrin photosensitizers have long been encapsulated into liposomes for drug delivery, little is known about the membrane properties of liposomes with large amphiphilic porphyrin compositions. In this paper, a porphyrin-lipid conjugate was incorporated into liposomes formed of saturated or unsaturated lipids to study the membrane composition-dependent formation of highly ordered porphyrin J-aggregates and disordered aggregates. Porphyrin-lipid readily phase-separates in saturated membranes, forming J-aggregates that are destabilized during the ripple phase below the main thermal transition. Porphyrin-lipid J-aggregates are photostable with a photothermal efficiency of 54 ± 6%, comparable to gold. Even at high porphyrin-lipid compositions, porphyrin J-aggregates coexist with a minority population of disordered aggregates, which are photodynamically active despite being fluorescently quenched. For photothermal applications, liposome formulations that encourage porphyrin-lipid phase separation should be explored for maximum J-aggregation.

Photodynamic Therapy Versus Glucose for the Treatment of Telangiectasia: A Randomised Controlled Study in a Rabbit Ear Model.

OBJECTIVES: Telangiectasia is a common venous formation that mainly affects women and causes discomfort, including psychological distress. This study compared photodynamic therapy (PDT) with glucose for vessel sclerosis in a rabbit ear model. METHODS: Thirty-six ears of 18 rabbits were randomly divided into four groups: Group 1: only injection of Photogem (4 mg/mL); Group 2: only light (635 nm, 100 mW/cm2, 8 min, 48 J/cm2); Group 3: glucose 75% injection; Group 4: PDT procedure with injection of Photogem and illumination immediately after. Injections were made into the central ear artery. After injection or sham procedures, manual compression of the marginal vein was maintained for 8 min in all ears. Follow up was immediately after the procedures, and one and six days later. The percentage of length reduction of spider veins, the target vessels, was analysed in digital photographs with Image J software. Ear thermographs were made with a thermocamera device and average temperatures were collected for analysis. Ear biopsies were obtained after six days. Endothelium average, inflammation, fibrosis, necrosis, skin burn, and vascular thrombosis were assessed using a specific score. RESULTS: The mean vessel length reduction was 26% for Group 4, 2.4% for Group 3, .4% for Group 1, and 0 for Group 2, highlighting that in Group 4, the vessel lengths were significantly reduced compared with the other groups (p < .001). In the thermal analysis, in Group 3, the temperature was unchanged from the initial temperature and the central diameter vessel increased after six days, while, in Group 4, the temperature decreased and the vessels were not clearly detected, suggesting a reduction of the vessels and smaller infusion. Histology showed no difference among groups and one case of necrosis was found in Group 4. CONCLUSIONS: PDT was associated with significantly more target vessel sclerosis than glucose injection and controls.

Acceleration of newborn rats' development with the use of photobiomodulation and the near possibility of application in human premature babies.

Photobiomodulation was explored to find evidence of stimulation during the development of newborn rats. A light chamber device was used, and rat pups were divided into groups after birth. Investigation of the process' security was performed before the full experiment. Following a protocol of alternating illumination and mother's presence during the first 13 days, we observed that, in the group that received photobiomodulation, the pups opened their eyes faster, indicating earlier achievement of maturity. The rate of weight gain also indicates faster metabolic activity in the group that was photostimulated. This study is the first step toward the use of photobiomodulation for premature newborn human babies.

Photostimulation effects on chicken egg development: Perspectives on human newborn treatment.

It is well known that, under exposure to bright light, eggs tend to hatch earlier than control, without any damage to the birds. This report aims to systematically show the effect and establishes a proposal for a possible application to accelerate chicken egg formation, which could be extrapolated or adapted as a great advance in premature human newborns. Comparing several protocols, the experiments show that lower doses of light slowly delivered for 24 h promote higher efficiency in embryo development, increasing on average 25% of its size and more than 70% in weight when compared to the control. This weight difference shows promising results compared to rates of up to 17% found in the literature. These results can be a first step to reduce the stay of premature human infants in hospitals because light, when applied in very low doses, can accelerate the natural biological processes without risks.

A Multicenter Clinical Study of Expected and Unexpected Side Reactions During and After Skin Cancer Treatment by Photodynamic Therapy.

Photodynamic therapy (PDT) has been widely used for oncologic indications, especially nonmelanoma skin cancer such as superficial and nodular basal cell carcinoma (BCC). We present a multicenter clinical study conducted between 2012 and 2014 analyzing the adverse reactions during and after PDT with a standardized protocol in 866 lesions. A total of 728 patients with positive clinical and histopathological diagnosis for BCC with up to 2 cm diameter were treated. The procedure consisted of curettage and topical application of cream containing 20% methyl 5-aminolevulinate. The illumination (630 nm and 150 J/cm2) was performed 3 hours after the cream application. The expected and unexpected effects observed were pain, healing, and inflammatory reactions. The pain intensity was correlated with the anatomical localization of the lesion. The patients reported a higher intensity of pain in lesions located on the head and neck rather than on the trunk and limbs. The number of sessions also influenced the pain response. A total of 83% of patients showed perfect healing and the other 17% presented abnormal healing. PDT plays an important role in BCC because of its low cost, ease of use, and low rate of side effects.

PDT and emerging therapies for Actinic Keratosis-A resource letter.

Aktinic Keratosis is common and if left untreated may develop into life threatening squamous cell carcinoma. Therefore early intervention is the standard of care. While many treatments are available PDT continues to move to the for - front for this indication (Brito et al., 2016 [31]). Topical PS is commercially available that are able to reliably ablate these lesions. Innovative protocols including sunlight, large volume LED arrays and maneuvers to improve treatment parameters and cosmesis continue to make this a worldwide treatment of choice for AK.

Photodynamic therapy: Progress toward a scientific and clinical network in Latin America.

Cancer is one of the major challenges for Latin America health services, since the skin cancer is the most frequent lesion. This manuscript addresses an initiative for the treatment of basal cell carcinomas (BCC) by photodynamic therapy (PDT) based on a government-funded national program in Brazil. The program provides clinical training and facilitates access to drugs/equipment and significantly reduces PDT costs. It also lays foundations for the establishment of a Latin American research network to improve prevention, early detection and treatment of diseases. Centers have been established by direct contact (conferences, visits to healthcare facilities and official departments). A local training was divided into complementary theoretical and practical parts. This is an ongoing project that has involved 10 countries: Brazil, Bolivia Chile, Ecuador, El Salvador, Colombia, Cuba, Mexico, Peru and Venezuela, The initial results are encouraging and have provided assessment of Latin America patients relating, for example, the most common skin phototypes with incidence of BCC in such countries. The network is expected to produce relevant scientific information for PDT introduction in many countries. The experience acquired by local teams shall enable them to innovate PDT protocols and increase the number of skilled contributors/researchers to broaden knowledge on the ever-crescent PDT field in Latin America. The establishment of a collaboration network and introduction of other projects and experience exchange shall become an easier process with time. This PDT clinical research network is a start for the strengthening of Science in South Hemisphere countries.

Experience and BCC subtypes as determinants of MAL-PDT response: preliminary results of a national Brazilian project.

Non-melanoma skin cancer is the most prevalent cancer type in Brazil and worldwide. Photodynamic therapy (PDT) is a noninvasive technique with excellent cosmetic outcome and good curative results, when used for the initial stages of skin cancer. A Brazilian program was established to determine the efficacy of methyl aminolevulinate (MAL)-PDT, using Brazilian device and drug. The equipment is a dual device that combines the photodiagnosis, based on widefield fluorescence, and the treatment at 630nm. A protocol was defined for the treatment of basal cell carcinoma with 20% MAL cream application. The program also involves the training of the medical teams at different Brazilian regions, and with distinct facilities and previous PDT education. In this report we present the partial results of 27 centers with 366 treated BCC lesions in 294 patients. A complete response (CR) was observed in 76.5% (280/366). The better response was observed for superficial BCC, with CR 160 lesions (80.4%), when compared with nodular or pigmented BCC. Experienced centers presented CR of 85.8% and 90.6% for superficial and nodular BCC respectively. A high influence of the previous doctor experience on the CR values was observed, especially due to a better tumor selection.

Probing conformational changes in orphan nuclear receptor: the NGFI-B intermediate is a partially unfolded dimer.

Human nerve growth factor-induced B (NGFI-B) is a member of the NR4A subfamily of orphan nuclear receptors (NRs). Lacking identified ligands, orphan NRs show particular co-regulator proteins binding properties, different from other NRs, and they might have a non-classical quaternary organization. A body of evidence suggests that NRs recognition of and binding to ligands, DNA, homo- and heterodimerization partners and co-regulator proteins involve significant conformational changes of the NR ligand-binding domains (LBDs). To shed light on largely unknown biophysical properties of NGFI-B, here we studied structural organization and unfolding properties of NGFI-B ligand (like)-binding domain induced by chemical perturbation. Our results show that NGFI-B LBD undergoes a two-state guanidine hydrochloride (GndHCl) induced denaturation, as judged by changes in the alpha-helical content of the protein monitored by circular dichroism spectroscopy (CD). In contrast, changes in the tertiary structure of NGFI-B LBD, reported by intrinsic fluorescence, reveal a clear intermediate state. Additionally, SAXS results demonstrate that the intermediate observed by intrinsic fluorescence is a partially folded homodimeric structure, which further unfolds without dissociation at higher GndHCl concentrations. This partially unfolded dimeric assembly of NGFI-B LBD might resemble an intermediate that this domain access momentarily in the native state upon interactions with functional partners.