Photosensitizer Concentration Research Articles

Photoacoustic nanodroplets for oxygen enhanced photodynamic therapy of cancer

Photodynamic therapy (PDT) is a well-known cancer therapy that utilizes light to excite a photosensitizer and generate cytotoxic reactive oxygen species (ROS). The efficacy of PDT primarily depends on the photosensitizer and oxygen concentration in the tumor. Hypoxia in solid tumors promotes treatment resistance, resulting in poor PDT outcomes. Hence, there is a need to combat hypoxia while delivering sufficient photosensitizer to the tumor for ROS generation. Here we showcase our unique theranostic perfluorocarbon nanodroplets as a triple agent carrier for oxygen, photosensitizer, and indocyanine green that enables light triggered spatiotemporal delivery of oxygen to the tumors. We evaluated the characteristics of the nanodroplets and validated their ability to deliver oxygen via photoacoustic monitoring of blood oxygen saturation and subsequent PDT efficacy in a murine subcutaneous tumor model. The imaging results were validated with an oxygen sensing probe, which showed a 9.1 fold increase in oxygen content inside the tumor, following systemic administration of the nanodroplets. These results were also confirmed with immunofluorescence. In vivo studies showed that nanodroplets held higher rates of treatment efficacy than a clinically available benzoporphyrin derivative formulation. Histological analysis showed higher necrotic area within the tumor with perfluoropentane nanodroplets. Overall, the photoacoustic nanodroplets can significantly enhance image-guided PDT and has demonstrated substantial potential as a valid theranostic option for patient-specific photodynamic therapy-based treatments.

Investigation of powerful fungicidal activity of tetra-cationic platinum(II) and palladium(II) porphyrins by antimicrobial photodynamic therapy assays

This manuscript reports enhanced antimicrobial photoinactivation using tetra-cationic porphyrins with peripheral platinum(II) and palladium(II) complexes against fungal dermatophyte strains. Six different positively charged porphyrins were used and applied in antimicrobial photodynamic therapy experiments (aPDT) against dermatophyte fungi colonies. The microbiological tests were conducted with an adequate concentration of photosensitizer (PS) under white-light irradiation for 120 min and the most effective PS meta isomer 3PtP significantly reduced the concentration of viable fungal colony. In this way, tetra-cationic porphyrins containing platinum(II)-bipyridyl complexes may be promising fungicidal aPDT agents with potential applications in future clinical cases.

Pilot-scale field demonstration of a hybrid nanofiltration and UV-sulfite treatment train for groundwater contaminated by per- and polyfluoroalkyl substances (PFASs)

Previous laboratory scale studies indicate nanofiltration (NF) and UV-sulfite photochemical treatments as promising technologies for the removal and destruction, respectively, of per- and polyfluoroalkyl substances (PFASs) from contaminated water. This study reports on a field demonstration of a pilot-scale hybrid NF and UV-sulfite treatment train for the remediation of 12 PFASs detected in groundwater impacted by aqueous film-forming foam (AFFF) at a U.S. Department of Defense installation. For most of the detected PFASs, NF rejection was consistently ≥ 95% over a 30-day field trial when operating at 90% total permeate recovery. Rejection of short-chain perfluorosulfonic acids (PFSAs) by NF decreased when recoveries increased from 90 to 97%; tests with a reverse osmosis (RO) membrane showed ≥ 99% rejection of all PFASs regardless of increasing recovery. UV treatment of the NF reject following 90% permeate recovery resulted in variable destruction of individual PFASs, with rates also being dependent on pH and the identity and concentration of UV photosensitizer. Rates of perfluorocarboxylic acid (PFCA) degradation were greater than those measured for PFSAs and perfluoroalkyl acid (PFAA) precursors and were independent of perfluoroalkyl chain length. In contrast, rates of PFSA degradation increased with increasing chain length. Consistent levels of PFAS degradation by UV-sulfite were observed during a 30-day demonstration experiment in NF reject water amended with 10 mM sulfite and adjusted to pH 11.2. Collectively, > 75% of the detected PFAS mass in the NF reject was destroyed after 4 h of UV treatment, increasing to > 90% after 8 h of treatment. An analysis of electrical energy inputs for the hybrid NF/UV-sulfite treatment train showed energy per order magnitude (EE/O) requirements ranging from ≤ 13.1 kWh/m3 for PFCAs and 14.1 kWh/m3 for PFOS to values > 100 kWh/m3 for more recalcitrant short-chain PFSA analogues. The UV reactor and water-cooling system were the major contributors to overall energy requirements and represent the greatest opportunities for improving efficiency of the technology.

An optical fiber integrated optoelectrode for the photoelectrochemical detection

A novel optical fiber integrated optoelectrode was proposed and miniatured photoelectrochemical (PEC) sensor was realized. In the structure, transparent conductive oxide indium-tin-oxide (ITO) film and photocatalytic material are coated outside of one end of the optical fiber. This tiny optoelectrode first simultaneously realizes the light-guiding ability and the microelectrode function of electroanalysis. Specifically, the detection of trace nitrite is realized by PEC process of the optical fiber/ITO/BiOI optoelectrode. The integrated optoelectrode shows remarkable electrochemical performance, and the sensor has notable PEC detection ability. At the optimal photosensitizer concentration, the optoelectrode sensor has a linear range of 1 nM–1 μM and a low detection limit of 5 × 10−10 M for the nitrite sensing. Due to the advantages of integration, fast detection, high sensitivity, and simple operation, the proposed optoelectrode has great potentials in a variety of fields, such as all-fiber integrated devices and various biochemical microanalyses systems.

Potentiation of Antimicrobial Photodynamic Therapy by Curcumin-loaded Graphene Quantum Dots.

Increasing resistance to existing antibiotics by microbes is currently the biggest dilemma. Antimicrobial photodynamic therapy is a promising alternative for the treatment of multidrug-resistant infections. The aim of the current study was to fabricate graphene quantum dots loaded with curcumin as photosensitizer for improved antimicrobial photodynamic therapy. The study involved fabrication of blank and curcumin-loaded graphene quantum dots, their characterizations (TEM, UV-visible and fluorescence emission spectra), cytotoxicity assay, ROS assay and investigation of enhanced antimicrobial photodynamic effect against resistant microbes. The fabrication of blank and loaded graphene quantum dots was confirmed by the observation of peak shift and changes in peak intensity of blank graphene quantum dots, curcumin alone compared with curcumin-loaded graphene quantum dots in UV-visible and fluoresce emission spectra. Cytotoxicity assay showed that 100 µm concentration was not toxic to NIH/3t3 fibroblasts. In ROS assay, the curcumin-loaded formulation showed three-fold increase in ROS production. Blue-light (405 nm) irradiance of 30 J cm-2 and photosensitizer concentration of 100 µm showed ~3.5 log10 enhanced CUF reduction against Pseudomonas aeruginosa, MRSA, Escherichia coli and Candida albicans. In conclusion, curcumin-loaded graphene quantum dots shoed enhanced antimicrobial photodynamic effects and can be used as an alternative effective treatment for resistant infections.

Kinetic analysis of the partial synthesis of artemisinin: Photooxygenation to the intermediate hydroperoxide

The price of the currently best available antimalarial treatment is driven in large part by the limited availability of its base drug compound artemisinin. One approach to reduce the artemisinin cost is to efficiently integrate the partial synthesis of artemisinin starting from its biological precursor dihydroartemisinic acid (DHAA) into the production process. The optimal design of such an integrated process is a complex task that is easier to solve through simulations studies and process modelling. In this article, we present a quantitative kinetic model for the photooxygenation of DHAA to an hydroperoxide, the essential initial step of the partial synthesis to artemisinin. The photooxygenation reactions were studied in a two-phase photo-flow reactor utilizing Taylor flow for enhanced mixing and fast gas-liquid mass transfer. A good agreement of the model and the experimental data was achieved for all combinations of photosensitizer concentration, photon flux, fluid velocity and both liquid and gas phase compositions. Deviations between simulated predictions and measurements for the amount of hydroperoxide formed are 7.1 % on average. Consequently, the identified and parameterized kinetic model is exploited to investigate different behaviors of the reactor under study. In a final step, the kinetic model is utilized to suggest attractive operating windows for future applications of the photooxygenation of DHAA exploiting reaction rates that are not affected by mass transfer limitations.

Organic Light‐Emitting Diodes as an Innovative Approach for Treating Cutaneous Leishmaniasis

AbstractAntimicrobial photodynamic therapy (APDT) has been studied as a noninvasive therapy for treating cutaneous leishmaniasis to overcome challenges with current treatment, such as toxicity, resistance, and need for in‐patient hospital treatment. Organic light‐emitting diodes (OLEDs) have emerged as an attractive technology that can provide wearable light‐emitting materials that are conformable to human skin. This makes OLEDs ideal candidates for APDT by light‐bandages for ambulatory care. In this work, suitable OLEDs are successfully developed to match the absorbance of three photosensitizers: methylene blue, new methylene blue, and 1,9‐dimethyl‐methylene blue to inactivate two Leishmania species in vitro: Leishmania major and Leishmania amazonensis. Parasites are treated either by LED (20 mW cm−2) or OLED (6.5 mW cm−2) at increasing photosensitizer concentrations at a radiant exposure of 50 J cm−2. 1,9‐Dimethyl‐methylene blue is the most potent photosensitizer, killing both strains at nanomolar concentrations. The effect of different intensities from the OLEDs (0.7, 1.5, and 6.5 mW cm−2) are also explored and it is shown that effective killing of Leishmania occurs even at a very low intensity. These findings demonstrate the great potential of OLEDs as a new approach for ambulatory treatment of cutaneous leishmaniasis by APDT.

Pyrazole-pyridinium porphyrins and chlorins as powerful photosensitizers for photoinactivation of planktonic and biofilm forms of E. coli

In nature, microorganisms can form highly structured complexes designed as biofilms, that cause severe and chronic infectious in humans. The formation of biofilms provides microbes many advantages, resulting in a higher tolerance to the conventional treatments. Antimicrobial photodynamic therapy (aPDT) is an efficient therapeutic alternative to eradicate microbial cells, which combines a photosensitizer (PS), like porphyrins (Pors) or chlorins (Chls), oxygen and light to induce the formation of reactive oxygen species (ROS) that can lead to cell damage and even death. For this purpose, cationic Pors and Chls (1a and 2a, respectively) bearing 4-(1H-pyrazol-3-yl)pyridinium groups were synthesized and characterized, and their aPDT efficiency investigated against planktonic and biofilm forms of Escherichia coli, a Gram-negative bacterium. The obtained results demonstrate that Por 1a and Chl 2a exhibit high aPDT efficacy towards planktonic and biofilm forms of E. coli. For the planktonic cells, both PSs at 2.0 μM caused a bacterial photoinactivation till the detection limit of the method, after 30 min of red light irradiation at an irradiance of 14 mW cm−2 (25.2 J cm−2). However, under white light (25 mW cm−2), the aPDT efficiency of Por 1a was improved and completely inactivated E. coli after 10 min (15 J cm−2) of treatment. On the other hand, the photodynamic efficiency of Chl 2a at 2.0 μM has similar behaviour under the different light conditions. For the biofilm's assays, a complete photoinactivation was obtained by increasing the concentration of 1a and 2a to 10 and 5.0 μM, respectively, after 60 min under white light at an irradiance of 100 mW cm−2. The compound 1a exhibited a higher antimicrobial efficiency against the planktonic cells of E. coli, while 2a derivative was more efficient towards biofilms. This photodynamic efficiency can be related with the higher levels of 1O2 produced by 1a, as well as with the higher absorption in the red region exhibited by 2a, that might allow a better penetration in the biofilm structure. The potential of theses PSs is magnified with the low PS concentration and low light doses required, when compared with other cationic PSs, to achieve the total inactivation for both planktonic and biofilm forms of E. coli, which is a clear advantage for a clinical application.

Phenothiazinium Photosensitizers Associated with Silver Nanoparticles in Enhancement of Antimicrobial Photodynamic Therapy.

Antimicrobial photodynamic therapy (APDT) and silver nanoparticles (AgNPs) are known as promising alternatives for the control of microorganisms. This study aims to evaluate the antifungal activity of APDT, particularly by using the association of low concentrations of phenothiazinium photosensitizers (PS) methylene blue (MB), new methylene blue N (NMBN), and new methylene blue N Zinc (NMBN-Zn) in association with biosynthesized AgNPs. The AgNPs were characterized by UV-Vis spectrophotometry, transmission electron microscopy, and the dynamic light scattering method. The minimum inhibitory concentration of compounds in APDT against Candida albicans and Fusarium keratoplasticum was obtained and the Fractional Inhibitory Concentration Index determined the antifungal effect. The toxicity of compounds and associations in APDT were evaluated in Galleria mellonella. The AgNPs presented a surface plasmon band peak at 420 nm, hydrodynamic diameter of 86.72 nm, and zeta potential of −28.6 mV. AgNPs-PS showed a wider and displaced plasmon band peak due to PS ligands on the surface and decreased zeta potential. AgNPs-NMBN and AgNPs-NMBN-Zn associations presented synergistic effect in APDT with 15 J cm−2 against both fungi and did not show toxicity to G. mellonella. Hence, the enhancement of antifungal activity with low concentrations of compounds and absence of toxicity makes APDT with AgNPs-PS a promising therapeutic alternative for fungal infections.

Induced photo-cytotoxicity on prostate cancer cells with the photodynamic action of toluidine Blue ortho

BackgroundPhotodynamic therapy (PDT) has become an advantageous therapeutic approach for the treatment of select cancers and microbial infections. PDT generates toxic reactive oxygen species as an end product of the interaction between the photosensitizer and light with an appropriate wavelength. Toluidine blue ortho is a photosensitizer that is commonly used in the photodynamic treatment of bacterial infection and a promising photosensitizer for cancer treatment. This study aims to evaluate the potential photo-cytotoxicity of toluidine blue ortho-mediated photodynamic therapy on PC-3 prostate cancer cells. MethodsIn this study toluidine blue ortho-mediated photodynamic therapy was assessed on PC-3 cancer cells with various photosensitizer concentrations and light energy densities of the 655-nm diode laser. MTT analysis was used for the determination of the cytotoxicity on the cells and viability/cytotoxicity assay was used for live/dead cell staining after the applications. The mechanism of this application was further analyzed with the determination of intracellular reactive oxygen species and nitric oxide release. ResultsThe light applications and the photosensitizer alone did not inhibit the cell viability of PC-3 cells. 20 J/cm2 laser energy density together with 100 μM photosensitizer concentration resulted in maximum cancer cell death with a rate of approximately 89 %. The level of intracellular reactive oxygen species increased with the increasing parameters of the applications that resulted in more cell death. ConclusionThis study showed the successful anticancer activity of toluidine blue ortho upon irradiation with 655 nm of laser light against PC-3 cancer cells and it was mediated with the production of reactive oxygen species.

Lactuca sativa leaf extract concentration optimization using evolutionary strategy as photosensitizer for TiO2-filmed Grӓtzel cell

To enhance the power efficiency of a dye-sensitized solar cell (DSSC) or Grӓtzel cell, photosensitizer concentration must be fine-adjusted within the ultraviolet and near-infrared spectrum. In this study, evolutionary computing through genetic algorithm (GA) and evolutionary strategy (ES) was employed to determine the optimal combination of chlorophyll a and anthocyanin concentrated dyes extracted from cultivated Lactuca sativa var. Altima (green) and Rania (violet). ES configured with 0.6 selection rate, 0.08 Gaussian mutation rate, and 0.4 crossover rate generated the optimal dye concentration of 16.5% green and 83.5% violet yielding 24.093% efficiency in AM 1.5 sunlight intensity. It also exhibited the maximum short-circuit current (4.591 mA), open-circuit voltage (688.7 mV), filling factor (0.762), and power (3.162 mW). UV-Vis spectrophotometry confirmed that combining chlorophyll (663 nm) and anthocyanin (520 nm) pigments increases photon energy utilization. It is supported by the 2.39 eV optical energy bandgap and 2.009 Km−1 absorption coefficient of the ES-based cell. FTIR verified that no new bond or reaction was formed by combining pigments rather they coexist with each other allowing a broader light spectrum to excite the ground state electrons in the TiO2 layer. Thus, ES-combined dyes increased the efficiency by a factor of 9.965 and 2.299 from green and violet pigments respectively.

Revisiting Tetra-p-Sulphonated Porphyrin as Antimicrobial Photodynamic Therapy Agent

Photodynamic inactivation is known as a new antimicrobial photodynamic therapy (aPDT). It is based on the administration of a photosensitizer located in the bacterial/viral cell followed by exposure to light radiations (with a proper wavelength corresponding with the maximum value of absorption of the photosensitizer) that generate singlet oxygen or reactive oxygen species, which lead to the death of different microorganisms. This review will present an overview beyond the state-of-the-art of the photosensitizer types (based on tetra-p-sulphonated-phenyl porphyrin—TSPP, which is able to form cationic and J-aggregates forms at different pH values ((1–4) and concentrations around 10−5 M) and their applications of PDT for viruses, especially. The mechanism of dicationic and J-aggregates formation is presented in this paper, and the photophysical parameters have been collected and harmonized to support their behaviours. Studies on Herpes Simplex virus type 1 (HSV-1) are useful, because without the help of HSV-1, the COVID-19 virus may not be able to cause serious illness or death in humans. This method could be a new direction for COVID treatment and immunization, either to prevent infections or to develop photoactive fabrics (e.g., masks, suits, gloves) to disinfect surfaces, under artificial light and/or natural sunlight. The use of photodynamic therapy (PDT) can be an alternative approach against SARS-CoV-2 that deserves to be explored.

Computational simulation of low energy x-ray source for photodynamic therapy: a preliminary study

Photodynamic therapy is a therapeutic modality capable of selectively inducing cytotoxic effects in malignant cells. Such effects are obtained by using a laser or a lamp as a light source to irradiate a previously-delivered photosensitizer into the tumoral cells. Since clinical application of photodynamic therapy depends on light penetration, lasers and lamps can only be used for shallow tissue treatment. To overcome this limitation, x-ray induced photodynamic therapy has been recently proposed. The goal of this work is to investigate the x-ray interactions in a medium containing a homogeneous concentration of distinct photosensitizers. This is achieved by evaluating the relative doses and energy spectra, obtained at distinct depths by means of Monte Carlo simulations. Preliminary results for the relative dose showed a minor dose increase, of approximately 0.15%, when photosensitizers are used. In addition, x-ray interactions with the investigated photosensitizers mostly occur from photons with energies below 60 keV.

Estimation of fluorescence probing depth dependence on the distance between source and detector using Monte Carlo modeling.

Photosensitizer fluorescence emission during photodynamic therapy (PDT) can be used to estimate for in vivo photosensitizer concentration. We built a surface contact probe with 405nm excitation light source to obtain Photofrin fluorescence signal during clinical PDT. The probe was equipped with multiple detector fibers that were located at distances between 0.14 to 0.87 cm laterally from the excitation source fiber. In this study, we investigated the probing depth of fluorescence in biological tissue with different source-detector separation using our contact probe setup. We used Monte Carlo method to simulate the 405nm excitation light and 630nm fluorescence probing depth at various source and detector (SD) separations. The results provided insight to the most probable depth of origin of detected fluorescence at each SD separation and help to understand the in vivo depth distribution of clinically measured Photofrin concentration.

Determination of the distribution of drug concentration and tissue optical properties for ALA-mediated anal photodynamic therapy.

PDT efficacy depends on the availability and dynamic interactions of photosensitizer, light, and oxygen. Tissue optical properties influence the delivered light dose and impact PDT outcome. In-vivo measurements of tissue optical properties and photosensitizer concentration enable determination of explicit and implicit dose factors affecting PDT and helps to understand the underlying biophysical mechanism of PDT. In this study, we measure tissue optical properties (absorption μa (λ) and scattering μs' (λ) coefficients) and PpIX concentration in tissue simulating liquid phantoms with a geometry that resembles anal canal. In-vivo light fluence rate and photosensitizer fluorescence of 405nm excitation light source were acquired using a dual-motor continuous wave transmittance spectroscopy system. We characterized the tissue optical properties correction factor of fluorescence signal using a series of tissue simulating phantoms with known PpIX concentrations and with absorption coefficient between 0.1 - 0.9 cm-1 and reduced scattering coefficient between 5 - 40 cm-1. The results demonstrated that our spectroscopy system could determine the distribution of tissue optical properties and PPIX concentration during anal PDT.

Attritional evaluation of lipophilic and hydrophilic metallated phthalocyanines for oncological photodynamic therapy

Background and aimOncological photodynamic therapy (PDT) relies on photosensitizers (PSs) to photo-oxidatively destroy tumor cells. Currently approved PSs yield satisfactory results in superficial and easy-to-access tumors but are less suited for solid cancers in internal organs such as the biliary system and the pancreas. For these malignancies, second-generation PSs such as metallated phthalocyanines are more appropriate. Presently it is not known which of the commonly employed metallated phtahlocyanines, namely aluminum phthalocyanine (AlPC) and zinc phthalocyanine (ZnPC) as well as their tetrasulfonated derivatives AlPCS4 and ZnPCS4, is most cytotoxic to tumor cells. This study therefore employed an attritional approach to ascertain the best metallated phthalocyanine for oncological PDT in a head-to-head comparative analysis and standardized experimental design. MethodsZnPC and AlPC were encapsulated in PEGylated liposomes. Analyses were performed in cultured A431 cells as a template for tumor cells with a dysfunctional P53 tumor suppressor gene and EGFR overexpression. First, dark toxicity was assessed as a function of PS concentration using the WST-1 and sulforhodamine B assay. Second, time-dependent uptake and intracellular distribution were determined by flow cytometry and confocal microscopy, respectively, using the intrinsic fluorescence of the PSs. Third, the LC50 values were established for each PS at 671 nm and a radiant exposure of 15 J/cm2 following 1-h PS exposure. Finally, the mode of cell death as a function of post-PDT time and cell cycle arrest at 24 h after PDT were analyzed. ResultsIn the absence of illumination, AlPC and ZnPC were not toxic to cells up to a 1.5-μM PS concentration and exposure for up to 72 h. Dark toxicity was noted for AlPCS4 at 5 μM and ZnPCS4 at 2.5 μM. Uptake of all PSs was observed as early as 1 min after PS addition to cells and increased in amplitude during a 2-h incubation period. After 60 min, the entire non-nuclear space of the cell was photosensitized, with PS accumulation in multiple subcellular structures, especially in case of AlPC and AlPCS4. PDT of cells photosensitized with ZnPC, AlPC, and AlPCS4 yielded LC50 values of 0.13 μM, 0.04 μM, and 0.81 μM, respectively, 24 h post-PDT (based on sulforhodamine B assay). ZnPCS4 did not induce notable phototoxicity, which was echoed in the mode of cell death and cell cycle arrest data. At 4 h post-PDT, the mode of cell death comprised mainly apoptosis for ZnPC and AlPC, the extent of which was gradually exacerbated in AlPC-photosensitized cells during 8 h. ZnPC-treated cells seemed to recover at 8 h post-PDT compared to 4 h post-PDT, which had been observed before in another cell line. AlPCS4 induced considerable necrosis in addition to apoptosis, whereby most of the cell death had already manifested at 2 h after PDT. During the course of 8 h, necrotic cell death transitioned into mainly late apoptotic cell death. Cell death signaling coincided with a reduction in cells in the G0/G1 phase (ZnPC, AlPC, AlPCS4) and cell cycle arrest in the S-phase (ZnPC, AlPC, AlPCS4) and G2 phase (ZnPC and AlPC). Cell cycle arrest was most profound in cells that had been photosensitized with AlPC and subjected to PDT. ConclusionsLiposomal AlPC is the most potent PS for oncological PDT, whereas ZnPCS4 was photodynamically inert in A431 cells. AlPC did not induce dark toxicity at PS concentrations of up to 1.5 μM, i.e., > 37 times the LC50 value, which is favorable in terms of clinical phototoxicity issues. AlPC photosensitized multiple intracellular loci, which was associated with extensive, irreversible cell death signaling that is expected to benefit treatment efficacy and possibly immunological long-term tumor control, granted that sufficient AlPC will reach the tumor in vivo. Given the differential pharmacokinetics, intracellular distribution, and cell death dynamics, liposomal AlPC may be combined with AlPCS4 in a PS cocktail to further improve PDT efficacy.

Influence of two photodynamic therapy sessions and different photosensitizers on the bond strength of glass-fiber posts in different regions of intraradicular dentin

Although photodynamic therapy associated with photosensitizers can promote microbial reduction, studies evaluating the consequences of two photodynamic therapy sessions associated with different photosensitizers on the bond strength of glass-fiber posts to endodontically treated intraradicular dentin are scarce. This in vitro study aimed to investigate the influence of two photodynamic therapy sessions using methylene blue or curcumin photosensitizers on the bond strength of glass-fiber posts to intraradicular dentin in different root thirds. Seventy-two teeth were divided into 9 experimental groups according to photosensitizer type, concentration and light-activation: Control - deionized water; Methylene blue 50 mg/L; Methylene blue 50 mg/L + laser; Methylene blue 100 mg/L; Methylene blue 100 mg/L + laser; Curcumin 500 mg/L; Curcumin 500 mg/L + LED; Curcumin 1000 mg/L; and Curcumin 1000 mg/L + LED. Push-out bond strength of the fiber posts to endodontically treated dentin was evaluated using a universal test machine (n = 8). Bond strength data underwent Kruskal-Wallis test, followed by Dunn test for comparison between treatments, and Friedman test for comparison between thirds (α = 0.05). Illustrative scanning electron microscopy images were obtained to qualify the failure mode. Curcumin at higher concentration, activated or not by blue LED, decreased the bond strength values in the apical region when compared with the control group (P < 0.05). There was no difference between two photodynamic therapy sessions using methylene blue photosensitizer (activated or not) and the control group regardless of concentrations and root canal depth evaluated (P > 0.05). Regarding intraradicular depth, the different thirds showed no statistical difference on bond strength values (P > 0.05). All experimental groups presented predominance of mixed-type failure, excepting the methylene blue group at higher concentration activated by red laser, and the curcumin photosensitizer at both concentrations activated by blue LED. Methylene blue at a 50 mg/L concentration can be applied in two PDT sessions, after biomechanical preparation and before glass-fiber post luting, as it presents no influence on root dentin bond strength in in vitro conditions.

Cationic Pyrrolidine/Pyrroline-Substituted Porphyrins as Efficient Photosensitizers against E. coli.

New porphyrin–pyrrolidine/pyrroline conjugates were prepared by revisiting 1,3-dipolar cycloaddition reactions between a porphyrinic azomethine ylide and a series of dipolarophiles. Cationic conjugates obtained by alkylation of the pyrrolidine/pyrroline cycloadducts showed ability to generate singlet oxygen and to produce iodine in presence of KI when irradiated with visible light. Some of the cationic derivatives showed photobactericidal properties towards a Gram-negative bioluminescent E. coli. In all cases, these features were significantly improved using KI as coadjutant, allowing, under the tested conditions, the photoinactivation of the bacterium until the detection limit of the method with a drastic reduction of the required photosensitizer concentration and irradiation time. The obtained results showed a high correlation between the ability of the cationic porphyrin derivative to produce singlet oxygen and iodine and its E. coli photoinactivation profile.

Recent Advances in Photosensitizers as Multifunctional Theranostic Agents for Imaging-Guided Photodynamic Therapy of Cancer.

In recent years tremendous effort has been invested in the field of cancer diagnosis and treatment with an overall goal of improving cancer management, therapeutic outcome, patient survival, and quality of life. Photodynamic Therapy (PDT), which works on the principle of light-induced activation of photosensitizers (PS) leading to Reactive Oxygen Species (ROS) mediated cancer cell killing has received increased attention as a promising alternative to overcome several limitations of conventional cancer therapies. Compared to conventional therapies, PDT offers the advantages of selectivity, minimal invasiveness, localized treatment, and spatio-temporal control which minimizes the overall therapeutic side effects and can be repeated as needed without interfering with other treatments and inducing treatment resistance. Overall PDT efficacy requires proper planning of various parameters like localization and concentration of PS at the tumor site, light dose, oxygen concentration and heterogeneity of the tumor microenvironment, which can be achieved with advanced imaging techniques. Consequently, there has been tremendous interest in the rationale design of PS formulations to exploit their theranostic potential to unleash the imperative contribution of medical imaging in the context of successful PDT outcomes. Further, recent advances in PS formulations as activatable phototheranostic agents have shown promising potential for finely controlled imaging-guided PDT due to their propensity to specifically turning on diagnostic signals simultaneously with photodynamic effects in response to the tumor-specific stimuli. In this review, we have summarized the recent progress in the development of PS-based multifunctional theranostic agents for biomedical applications in multimodal imaging combined with PDT. We also present the role of different imaging modalities; magnetic resonance, optical, nuclear, acoustic, and photoacoustic in improving the pre-and post-PDT effects. We anticipate that the information presented in this review will encourage future development and design of PSs for improved image-guided PDT for cancer treatment.

A unique self-reporting photosensitizer enabling simultaneous photodynamic therapy and real-time monitoring of phototheranostic process in a dynamic dual-color mode.

Phototheranostics has attracted great interest in cancer therapy. Small-molecule self-reporting photosensitizers, one kind of idea agent in phototheranostics, enables simultaneous photodynamic therapy (PDT) and feedback of therapeutic efficacy. However, previous such photosensitizers exclusively employed the change of single emission to monitor cell death, which can be disturbed by variations in photosensitizer concentration and the excitation intensity. Herein, we report a unique self-reporting photosensitizer TPA-3PyA+ constructed from a twisted triphenylamine unit (TPA), three benzene ring units and three cyanovinyl-pyridinium units (PyA) for PDT and its real-time monitoring in a dynamic dual-color mode. TPA-3PyA+ possesses a rotatable electron donor-π bridge-electron acceptor framework and exhibits high singlet oxygen quantum yield (124%) and a twisted intramolecular charge transfer (TICT) effect. TPA-3PyA+ not only enables effective staining of cancer cells with dual-color fluorescence due to the TICT effect but also shows excellent PDT performance. The simultaneous change in emission color, intensity and intracellular location of TPA-3PyA+ during cell death allows it to self-report cell death. Moreover, the change of dual-emission color allows distinguishing living and dead cells and effectively avoids interference in previous single-emission self-reporting photosensitizers. This work highlights the great potential of a self-reporting photosensitizer with dual-color emissions for efficient feedback of theranostics.