Photodynamic Dyes Research Articles

Photoinduced Toxicity Caused by Gold Nanozymes and Photodynamic Dye Encapsulated in Submicron Polymer Shell

AbstractThe development of nanozymes, artificial enzymes made from inorganic nanoparticles, is widely studied due to their affordability, durability, and strength. Gold nanoparticles (AuNPs) are employed to imitate peroxidase, glucose oxidase, lactate oxidase, superoxide dismutase, and catalase. The last one transforms intracellular hydrogen peroxide into molecular oxygen, whose deficiency is characteristic of the hypoxic tumor microenvironment. Thus, gold nanoparticles are thought to enhance the overall effectiveness of photodynamic therapy. However, the enzyme‐like activity of nanoparticles rapidly decreases in biological media, due to the aggregation and formation of the so‐called “protein corona”. In this study, polymeric submicrocapsules loaded with AuNPs and a photodynamic dye are fabricated via Layer‐by‐Layer (LbL) assembly. The enhancement of photodynamic treatment efficacy by in situ production of oxygen by the catalase‐like effect of AuNPs is investigated. Polymeric capsules are thoroughly characterized in terms of physicochemical and catalytic properties, and as a proof of concept, their therapeutic potential is evaluated in vitro. Furthermore, encapsulated AuNPs shows significantly lower aggregation both upon storage and during the reaction course. The results shows that the polymer capsules, containing AuNPs and photodynamic dye, show significantly higher light‐induced cytotoxicity in comparison to the individual photodynamic dye, suggesting a synergistic effect between the formation of molecular oxygen by catalase‐like gold nanozymes and photodynamic action.

Antimicrobial Personal Protection Clothing: Development of Visible Light Activated Antimicrobial Coatings for Nonwoven Polypropylene Fibers

AbstractDuring the COVID‐19 pandemic, the use of polypropylene fleece‐based personal protection equipment (PPE) increased significantly to over ten million tons. Typically, most PPEs are discarded after a single use, to prevent self‐infection of users and spread of infectious agents. However, in order to minimize plastic waste without compromising the protective properties of PPE, it is crucial to explore new reusable or longer‐lived materials. Here, a visible light‐activatable antimicrobial photodynamic dye coating for PPEs is presented. In this context, coating with thiomorpholino‐methylene blue (TMB), derived from methylene blue by introducing two thiomorpholine units, is found to show high antibacterial activity. TMB is integrated into rotary printing suspension, a commercial nitrocellulose‐based printing matrix. The concentration of TMB in adhesive is optimized, and found that 5% TMB is suitable for coating PPE, for reducing the number of Gram‐positive and ‐negative bacteria by 99.99% after 6 h of white light irradiation. Bacterial filtration efficiency and breathability tested according to EN 14683, confirmed that TMB coating does not affect the filter performance. Thus, this antimicrobial photodynamic dye coating technique offers a promising solution for a safer and extended use of PPE, and reduction of plastic waste generated by PPEs.

NaYF4: Yb,Er Upconversion Nanoparticles for Imaging: Effect on Red Blood Cells

(1) Background: Upconversion nanoparticles (UCNPs) are a promising tool for biological tissue structure visualization and photodynamic therapy (PDT). The luminescence of such NPs is excited in the spectrum’s near-infrared (NIR) region, while the NPs luminesce in the visible region. Conjugating such NPs with photodynamic dyes that absorb their luminescence makes it possible to increase the depth at which PDT is performed. (2) Methods: We conducted a comprehensive study on the possibility of using NaYF4:Er:Yb UCNPs in vivo for imaging and PDT. The NPs were synthesized by a hydrothermal method. The synthesis of NPs with a size of 80 nm and hexagonal structure was demonstrated. (3) Results: The accumulation of NPs in organs after their intravenous injection into rats was studied. The effect of NPs on the shape, size, and degree of aggregation of red blood cells (RBC) was also investigated. (4) Conclusions: The possibility of luminescent visualization of NPs in histological sections and their subcutaneous distribution is demonstrated. All investigated particles showed moderate toxicity, causing mostly reversible changes.

Killing three birds with one stone: Multi-stage metabolic regulation mediated by clinically usable berberine liposome to overcome photodynamic immunotherapy resistance

Nowadays, photodynamic therapy (PDT) has become a novel effect modality for cancer therapy. But, facing the extremely hypoxic tumor microenvironment, the efficacy of PDT is still impaired owing to the limited reactive oxygen species (ROS) production. Moreover, after PDT, the overexpression of programmed cell death-ligand 1 (PD-L1) and indoleamine-2,3-dioxygenase-1 (IDO1) could trigger the following impaired T cell infiltration and the further lowered anti-tumor immunity mediated by T cells. Regrettably, up to now, no simple nanosystem could solve these defects of PDT simultaneously and economically. To ameliorate such a situation, we rationally designed and prepared clinically usable hypoxia reversing berberine liposome (BBR@IR68-Lip) with PD-L1 and IDO1 dual-depression capacity simultaneously to overcome photodynamic immunotherapy resistance. In this nanosystem, BBR@IR68-Lip was constructed by using near-infrared photodynamic dye IR68 chemically modified DSPE-PEG2000 with tumor-targeting capacity as liposome component to encapsulate berberine (BBR) as a novel tumor oxygen and immune microenvironment regulation drug. Owing to the tumor-targeting capacity of IR68-Lip, the accumulation of BBR in tumors further reversed tumor hypoxia, depressed PD-L1 expression, and lowered IDO1 expression via metabolic regulation, which then lead to enhanced ROS generation and amplified T cell infiltration in CT26 tumors. To sum up, in this study, we presented a simple, safe, and clinically usable nanoplatform with ideal tumor re-oxygenation, PD-L1, and IDO1 immune pathways dual-regulation capacity to overcome photodynamic immunotherapy resistance, which may be potential for clinical cancer immunotherapy shortly.

Cascade two-stage tumor re-oxygenation and immune re-sensitization mediated by self-assembled albumin-sorafenib nanoparticles for enhanced photodynamic immunotherapy.

As a promising modality for cancer therapy, photodynamic therapy (PDT) still acquired limited success in clinical nowadays due to the extremely serious hypoxia and immunosuppression tumor microenvironment. To ameliorate such a situation, we rationally designed and prepared cascade two-stage re-oxygenation and immune re-sensitization BSA-MHI148@SRF nanoparticles via hydrophilic and hydrophobic self-assembly strategy by using near-infrared photodynamic dye MHI148 chemically modified bovine serum albumin (BSA-MHI148) and multi-kinase inhibitor Sorafenib (SRF) as a novel tumor oxygen and immune microenvironment regulation drug. Benefiting from the accumulation of SRF in tumors, BSA-MHI148@SRF nanoparticles dramatically enhanced the PDT efficacy by promoting cascade two-stage tumor re-oxygenation mechanisms: (i) SRF decreased tumor oxygen consumption via inhibiting mitochondria respiratory. (ii) SRF increased the oxygen supply via inducing tumor vessel normalization. Meanwhile, the immunosuppression micro-environment was also obviously reversed by two-stage immune re-sensitization as follows: (i) Enhanced immunogenic cell death (ICD) production amplified by BSA-MHI148@SRF induced reactive oxygen species (ROS) generation enhanced T cell infiltration and improve its tumor cell killing ability. (ii) BSA-MHI148@SRF amplified tumor vessel normalization by VEGF inhibition also obviously reversed the tumor immune-suppression microenvironment. Finally, the growth of solid tumors was significantly depressed by such well-designed BSA-MHI148@SRF nanoparticles, which could be potential for clinical cancer therapy.

Methylene blue applied to N95 respirators and medical masks for SARS-CoV-2 decontamination: What is the likelihood of inhaling methylene blue?

BackgroundGlobal shortage of personal protective equipment (PPE), as consequence of the COVID-19 global pandemic, has unmasked significant resource inequities prompting efforts to develop methods for safe PPE decontamination for reuse. The World Health Organization (WHO) in their Rational Use of PPE bulletin cited the use of a photodynamic dye, methylene blue, and light exposure as a viable option for N95 respirator decontamination. Because WHO noted that methylene blue (MB) would be applied to surfaces through which health care workers breathe, we hypothesized that little to no MB will be detectable by spectroscopy when the PPE is subjected to MB at supraphysiologic airflow rates.MethodsA panel of N95 respirators, medical masks, and cloth masks were sprayed with 5 cycles of 1,000 uM MB solution. Mask coupons were subjected to the equivalent of 120 L/min of 100% humidified air flow. Effluent gas was trapped in an aqueous solution and the resultant fluid was sampled for MB absorbance with a level of detection of 0.004 mg/m3.ResultsNo detectable MB was identified for any mask using Ultraviolet-Visible spectroscopy.ConclusionsAt 500-fold the amount of MB applied to N95 respirators and medical masks as were used for the decontamination study cited in the WHO Rational Use of PPE bulletin, no detectable MB was observed, thus providing safety evidence for the use of methylene blue and light exposure for mask decontamination.

Air-Filled Bubbles Stabilized by Gold Nanoparticle/Photodynamic Dye Hybrid Structures for Theranostics.

Microbubbles have already reached clinical practice as ultrasound contrast agents for angiography. However, modification of the bubbles’ shell is needed to produce probes for ultrasound and multimodal (fluorescence/photoacoustic) imaging methods in combination with theranostics (diagnostics and therapeutics). In the present work, hybrid structures based on microbubbles with an air core and a shell composed of bovine serum albumin, albumin-coated gold nanoparticles, and clinically available photodynamic dyes (zinc phthalocyanine, indocyanine green) were shown to achieve multimodal imaging for potential applications in photodynamic therapy. Microbubbles with an average size of 1.5 ± 0.3 μm and concentration up to 1.2 × 109 microbubbles/mL were obtained and characterized. The introduction of the dye into the system reduced the solution’s surface tension, leading to an increase in the concentration and stability of bubbles. The combination of gold nanoparticles and photodynamic dyes’ influence on the fluorescent signal and probes’ stability is described. The potential use of the obtained probes in biomedical applications was evaluated using fluorescence tomography, raster-scanning optoacoustic microscopy and ultrasound response measurements using a medical ultrasound device at the frequency of 33 MHz. The results demonstrate the impact of microbubbles’ stabilization using gold nanoparticle/photodynamic dye hybrid structures to achieve probe applications in theranostics.

Novel indocyanine green mediated antimicrobial photodynamic therapy in the management of chronic periodontitis - A randomized controlled clinico-microbiological pilot study

BackgroundThe use of scaling, root planing, antimicrobials, or antibiotics in the treatment of Chronic Periodontitis have proven beneficial in the past. The reduction in inflammatory markers and significant resolve in the clinical signs and symptoms and microbial loads evinced by a number of studies are a clear corroboration of the fact, but certain restraints utilizing these methods call for more effective ways of treating the disease. Later, lasers or photodynamic dyes used with the lasers like methylene blue or toluidine blue O have also not proven much efficacy and need further research. Hence the present pilot study is a step forward in this direction as it helps analyse the microbiological and clinical effects of indocyanine green antimicrobial photodynamic therapy an as adjunct to the non-surgical periodontal therapy in treating chronic periodontitis patients. Materials and methods30 patients diagnosed with generalized chronic periodontitis were treated with scaling and root planing alone - control sites; and indocyanine green antimicrobial photodynamic therapy in addition to scaling and root planing - experimental sites. 810 ​nm low level Gallium Aluminium Arsenide diode laser was used to activate the dye in the periodontal pockets of the experimental sites. Clinical parameters i.e. gingival index, plaque index, sulcus bleeding index, probing pocket depth and relative attachment level; and microbiological parameter i.e. the total viable anaerobic count were recorded at the inception and at 3- and 6-months post therapy. ResultsExperimental sites showed significantly greater amelioration in all inquired clinical parameters and microbiological parameter at the end of 3- and 6-months of therapy. ConclusionWhile the gold standard scaling and root planing remains, clinicians may also contemplate using the indocyanine green mediated antimicrobial photodynamic therapy as an adjunct to it. Also, it is a safer, cost effective, less arduous, and patient friendly means of treating the disease.

Calcium carbonate microparticles with embedded silver and magnetite nanoparticles as new SERS-active sorbent for solid phase extraction

The authors describe a dual-use sorbent for solid phase extraction (SPE) in combination with surface-enhanced Raman spectroscopy (SERS). The sorbent consists of calcium carbonate microparticles with incorporated silver nanoparticles (AgNPs) and magnetic nanoparticles (Fe3O4). It can be simply prepared, is cost-effective, disposable, and possesses high sorption capabilities together with a Raman enhancement of 109 in the best case. Following magnetic separation of the microsphere from the liquid sample, the sorbent matrix (CaCO3) is dissolved in acid so that the AgNPs and the analyte are released. This provides an optimal interaction between them and warrants a strong SERS signal. A new SPE-SERS protocol was worked out and applied to the following model analytes: Rhodamine 6G (a fluorescent dye; R6G), Photosens (a photodynamic dye), and sulfadimethoxine (an antibiotic). The first two possess a high Raman cross-section, while the last one displays comparatively low intrinsic Raman intensity. It is found that coating the surface of the sorbent with polyethyleneimine (a cationic polyelectrolyte) leads to a 2-fold increase in the sorption of Photosens (from 40% to 90%) and to a 6-fold enhancement of the SERS signal. The limits of detection for R6G, Photosens, and sulfadimethoxine (with 78%, 94%, and 41% sorption values, respectively) are 29 pM, 12 nM, and 69 nM, respectively. Raman enhancements are in the range between 106 and 109 depending on the analyte.

Systemic reduction of rice blast by means of photosensitizers

Systemic disease resistance of plants may be induced by exogenous reactive oxygen species or their sources. Certain compounds (photosensitizers) produce ROS at the expense of light energy. Of them, this study used photodynamic dyes bengal rose and methylene blue, which yield singlet oxygen, and mercaptopyridine-N-oxide, which yields hydroxyl radical. The goals were to find out whether they can systemically protect rice (Oryza sativa L.) from blast caused by the fungus Magnaporthe oryzae Conouch et Kohn and whether ROS is involved in defense mechanisms. The tested compounds were placed on the fourth (uppermost) leaf. When the fifth leaf developed (in approximately 7 days), it was inoculated with virulent fungal strain. We found that almost all the chemical treatments altered the fourth leaf and all of them reduced disease symptoms on the fifth leaf. Antioxidants combined with the tested substances compromised the disease control. Photosensitizers applied to the fourth leaf increased superoxide production in drop diffusates of healthy and, to larger extent, infected fifth leaf. In these diffusates, fungitoxicity also increased, which was diminished by antioxidants added to the diffusates. Besides, treatment with mercaptopyridine-N-oxide systemically weakened the endogenous antioxidative (H2O2-decomposing) activity of a diffusate. It is suggested that the oxidative burst in the treated leaves induced the systemic disease resistance, whose accomplishment might include the secondary oxidative burst in systemic leaves suppressing the pathogen’s development.

Photodynamic dye adsorption and release performance of natural zeolite

Clinoptilolite type of zeolite (CZ) is a promising material for biomedicine and pharmaceutics due to its non-toxicity, thermal stability, expanded surface area, and exceptional ability to adsorb various atoms and organic molecules into micropores. Using multiphoton microscopy, we demonstrated that individual CZ particles produce two-photon excited luminescence and second harmonic generation signal at femtosecond laser excitation, and adsorb photo-dynamically active dyes such as hypericin and methylene blue. Furthermore, the release of hypericin from CZ pores in the presence of biomolecules is shown, and CZ can be considered as an effective material for drug delivery and controlled release in biological systems. The results may open new perspectives in application of CZ in biomedical imaging, and introducing of the optical approaches into the clinical environment.

Localized Electric Field of Plasmonic Nanoplatform Enhanced Photodynamic Tumor Therapy

Near-infrared plasmonic nanoparticles demonstrate great potential in disease theranostic applications. Herein a nanoplatform, composed of mesoporous silica-coated gold nanorods (AuNRs), is tailor-designed to optimize the photodynamic therapy (PDT) for tumor based on the plasmonic effect. The surface plasmon resonance of AuNRs was fine-tuned to overlap with the exciton absorption of indocyanine green (ICG), a near-infrared photodynamic dye with poor photostability and low quantum yield. Such overlap greatly increases the singlet oxygen yield of incorporated ICG by maximizing the local field enhancement, and protecting the ICG molecules against photodegradation by virtue of the high absorption cross section of the AuNRs. The silica shell strongly increased ICG payload with the additional benefit of enhancing ICG photostability by facilitating the formation of ICG aggregates. As-fabricated AuNR@SiO2-ICG nanoplatform enables trimodal imaging, near-infrared fluorescence from ICG, and two-photon luminescence/photoacoustic tomography from the AuNRs. The integrated strategy significantly improved photodynamic destruction of breast tumor cells and inhibited the growth of orthotopic breast tumors in mice, with mild laser irradiation, through a synergistic effect of PDT and photothermal therapy. Our study highlights the effect of local field enhancement in PDT and demonstrates the importance of systematic design of nanoplatform to greatly enhancing the antitumor efficacy.

Antimicrobial light-activated materials: towards application for food and environmental safety.

To produce light-activated antimicrobial materials composed of the photodynamic dye phloxine B incorporated into paper or cellulose membranes and to investigate ability of these materials to decrease bacterial loads on their surfaces as well as on food surfaces that were in contact with these materials under illumination with regular white light. Antimicrobial cellulose-based materials with incorporated phloxine B were produced using a layer-by-layer deposition method. Antimicrobial properties of the materials were tested in model systems as well as for decontamination of food and food contact surfaces. Pseudomonas aeruginosa, Listeria monocytogenes and Bacillus anthracis were efficiently killed by exposure of the bacterial suspension to the dye-containing material under illumination with white light, but Salmonella Typhimurium and Escherichia coli O157:H7 were only partially affected. Application of the materials for decontamination of food surfaces artificially contaminated with L. monocytogenes was shown to be ineffective, while the self-decontamination of the material surface by exposure to white light resulted in eradication of L. monocytogenes cells from the material surface. The developed materials showed significant self-decontaminating ability when under illumination; however, decontamination of food surfaces in contact with the developed materials was not achieved. The study demonstrates the antibacterial activity of materials with incorporated photodynamic dyes when under illumination with regular-intensity white light. Possible uses of the light-activated antimicrobial materials for food processing, as food contact surfaces, and surfaces in public areas to prevent cross-contamination are discussed.

Study of diffusion of indocyanine green as a photodynamic dye into skin using backscattering spectroscopy

One of the lines of development of modern medicine is theranostics consisting in simultaneous diagnosis and laser treatment with the use of multifunctional agents such as fluorescent indocyanine green that has photodynamic and photothermal properties. Diffusion of indocyanine green dissolved in water and aqueous solutions of alcohols (glycerol, propylene glycol and ethanol) into the dermis is studied by using backscattering spectroscopy. The coefficients of the dye diffusion into the dermis are obtained for the first time by using these solvents.

Suppression of cucurbit scab on cucumber leaves by photodynamic dyes

The goal of this study was to test the ability of the photodynamic dyes bengal rose, toluidine blue and methylene blue to protect systemically cucumber plants from cucurbit scab. At the stage of one true leaf, water or aqueous solutions of the dyes were applied to the leaf as droplets. When the second leaf appeared and was fully developed, it was inoculated with a spore suspension of Cladosporium cucumerinum. It was found that all dyes (at 0.5–200 μM) significantly suppressed symptoms of the disease. The effect was preceded by development of local damage of the treated leaf. The degree of the damage as well as the disease suppression increased with dye concentration. Both indices were smaller if the plants were kept in darkness for the first day after the treatment. It is suggested that reactive oxygen photogenerated by dyes caused a local cell death, which induced resistance in distant leaves. The dyes tested, or their derivatives, may offer a base for novel disease resistance inducers.

Evaluation of the sensitivity of red blood cell markers to detect photodynamic membrane damage.

Photodynamic dyes have been used to investigate pathogen reduction methods in RBC suspensions, but treatment with sensitizers and light can produce unwanted membrane damage during routine blood bank storage. This study compares the relative sensitivity of three assays for detecting RBC membrane damage. RBCs were treated with dimethylmethylene blue and red light-emitting diode light under four conditions differing in photodynamic stringency and subsequently stored under refrigerated conditions for up to 42 days. Hemolysis, potassium release, and the apoptosis marker annexin V binding were assayed immediately after phototreatment and following storage. In terms of increasing sensitivity for detecting photodynamic RBC membrane damage was enhanced ion leakage >> hemolysis > annexin V binding. Although very stringent photodynamic treatment conditions generate annexin V-positive RBCs, the assay will not detect more subtle membrane damage that is readily detected by other well-established methods. In addition, many RBCs destined for photo-induced hemolysis later in storage are annexin V-negative throughout the storage period, suggesting that the two measures are not directly related.

PHOTOTOXICITY FROM SYSTEMIC SODIUM FLUORESCEIN

Purpose: To confirm the occurrence of phototoxicity due to systemic fluorescein in a dose consistent with retinal angiographic testing and to approximate the prevalence of this reaction in a small group of volunteers. Methods: Fourteen volunteers underwent a controlled challenge test by applying a topical sunscreen and exposing skin areas to direct sunlight before and after fluorescein administration. Results: Two subjects experienced marked cutaneous blanching erythema, mild vesiculation, and pain in sun-exposed areas within 1 hour of exposure. The reaction faded over a period of days without tanning. Conclusions: Consistent with its in vitro properties as a photodynamic dye, fluorescein may rarely act as a phototoxic agent in humans at doses employed for fluorescein retinal angiography. It is unclear why this reaction has not been reported more frequently, given the large number of patients undergoing this ophthalmic procedure annually. RETINA 20:370-373, 2000

Phototoxic Reactions Caused by Sodium Fluorescein

To report three cases of phototoxic reactions to intravenous fluorescein for retinal angiography and to describe provocative testing in a volunteer. Three patients with phototoxic reactions were interviewed, and one volunteer underwent a controlled challenge test by applying a potent sunscreen and exposing skin areas to direct sunlight before and after fluorescein administration. All patients experienced marked cutaneous erythema, edema, and pain to sun-exposed areas within 1 hour of exposure. The reaction faded during a variable period of time, and one case resulted in mild epidermal desquamation and prolonged discomfort. We noted minimal skin changes in the volunteer who was exposed to the sun before fluorescein administration; however, marked blanching erythema and pain were noted after fluorescein administration and sunlight. Consistent with its in vitro properties as a photodynamic dye, fluorescein may rarely act as a phototoxic agent in humans at doses employed for fluorescein angiography.

Viral inactivation in platelet concentrates

Although the current risk of posttransfusion infection is very low in North America and Western Europe, there continues to be considerable interest in measures to inactivate residual viruses in blood components. The human immunodeficiency virus is of greatest concern, but hepatitis C virus is also considered to be a significant problem. HTLV-I and -II and HBV may also be transmitted by transfusion, although infrequently. It is likely that effective inactivation methods will have to reduce viral titers by about 6 orders of magnitude, including both viruses found free in plasma and those in intracellular compartments. Although it would be most desirable to have a single procedure to inactivate viruses in all blood components, it appears that different methods may be required for plasma, red cells and platelets. To date, the most promising approach for platelets appears to be photochemical inactivation. In general, photoactive compounds fall into two major groups: photodynamic dyes which are activated by visible light and act by oxygen dependent generation of reactive molecular species; and ultraviolet-activated intercalating compounds which form covalent adducts with nucleic acids. We have found that photodynamic inactivators are unable to inactivate viruses in platelet concentrates without damaging the platelets. On the other hand, we have shown that aminomethyl trimethyl psoralen (AMT), when activated by long-wavelength ultraviolet light (UVA) can inactivate more than 5 logs of model viruses and HIV while platelet in vitro properties are maintained. Further, unlike photodynamic inactivators, AMT is able to inactivate cell-associated and intracellular viruses and also prevents the replication of integrated HIV genome sequences, as demonstrated by PCR.(ABSTRACT TRUNCATED AT 250 WORDS)

Light-Dependent and Independent Responses of Populations of German and Brownbanded Cockroaches (Orthoptera: Blattellidae) to Two Photodynamic Dyes

Populations of male German cockroaches, Blattella germanica (L.), and nymphs of brownbanded cockroaches, Supella longipalpa (F.), were confined in the dark and provided only with selected doses of one of two photodynamic dyes. At concentrations > 1 x 10-3 M , erythrosin B caused more mortality in both species than did rose bengal. Most (85%) cockroaches of both species were fed dye within 2.5 h after exposure to light. When German cockroach males were fed rose bengal at 3 x 10-3 M or erythrosin B at 5 x 10-3 M and confined in the dark, significant loss of body weight resulted. Mortality of cockroaches in the dark was delayed, with LT50’s of 106 and 75 h, respectively.