Role Of Photodynamic Therapy Research Articles

A hexanuclear Iridium(III) cluster for histidine-induced singlet oxygen and superoxide radicals generation

Photosensitizers (PSs) play key roles in photodynamic therapy (PDT). PDT is typically reliant on the local concentration of oxygen. A big challenge for PSs is to develop oxygen-independent photosensitizers, which can work well in hypoxic tumor microenvironment. In this piece of work, a hexanuclear Ir(III) cluster (Ir6) is highly selective towards histidine and histidine-rich (His-rich) proteins to form mononuclear Ir(III) complexes of [Ir(bpy)2(His)]. After the selective response to histidine or his-rich proteins, [Ir(bpy)2(His)] generates both singlet oxygen(1O2) and superoxide (O2−). This work opens an avenue for the potential application of Ir6 for type Ι and ΙΙ synergic photodynamic therapy.

Thiophene Stability in Photodynamic Therapy: A Mathematical Model Approach.

Thiophene-containing photosensitizers are gaining recognition for their role in photodynamic therapy (PDT). However, the inherent reactivity of the thiophene moiety toward singlet oxygen threatens the stability and efficiency of these photosensitizers. This study presents a novel mathematical model capable of predicting the reactivity of thiophene toward singlet oxygen in PDT, using Conceptual Density Functional Theory (CDFT) and genetic programming. The research combines advanced computational methods, including various DFT techniques and symbolic regression, and is validated with experimental data. The findings underscore the capacity of the model to classify photosensitizers based on their photodynamic efficiency and safety, particularly noting that photosensitizers with a constant rate 1000 times lower than that of unmodified thiophene retain their photodynamic performance without substantial singlet oxygen quenching. Additionally, the research offers insights into the impact of electronic effects on thiophene reactivity. Finally, this study significantly advances thiophene-based photosensitizer design, paving the way for therapeutic agents that achieve a desirable balance between efficiency and safety in PDT.

Modern Photodynamic Glioblastoma Therapy Using Curcumin- or Parietin-Loaded Lipid Nanoparticles in a CAM Model Study.

Natural photosensitizers, such as curcumin or parietin, play a vital role in photodynamic therapy (PDT), causing a light-mediated reaction that kills cancer cells. PDT is a promising treatment option for glioblastoma, especially when combined with nanoscale drug delivery systems. The curcumin- or parietin-loaded lipid nanoparticles were prepared via dual asymmetric centrifugation and subsequently characterized through physicochemical analyses including dynamic light scattering, laser Doppler velocimetry, and atomic force microscopy. The combination of PDT and lipid nanoparticles has been evaluated in vitro regarding uptake, safety, and efficacy. The extensive and well-vascularized chorioallantois membrane (CAM) of fertilized hen's eggs offers an optimal platform for three-dimensional cell culture, which has been used in this study to evaluate the photodynamic efficacy of lipid nanoparticles against glioblastoma cells. In contrast to other animal models, the CAM model lacks a mature immune system in an early stage, facilitating the growth of xenografts without rejection. Treatment of xenografted U87 glioblastoma cells on CAM was performed to assess the effects on tumor viability, growth, and angiogenesis. The xenografts and the surrounding blood vessels were targeted through topical application, and the effects of photodynamic therapy have been confirmed microscopically and via positron emission tomography and X-ray computed tomography. Finally, the excised xenografts embedded in the CAM were analyzed histologically by hematoxylin and eosin and KI67 staining.

Effect of photodynamic therapy with hypericin on the secretion of selected cytokines of colorectal cancer cells tested in vitro

Introduction and aim. Photodynamic therapy is a complex process involving the introduction of photosensitizers into the patient’s body and irradiation of them in order to destroy the lesion, and activate the immune system. An important role in photodynamic therapy is played by photobiochemical and physical mechanisms that affect the tumor vessels and lead to the death of the damaged cell. The aim of the study is to determine the effect of photodynamic therapy with the use of Hypericin (Hyp) on the secretion of selected cytokines by colorectal cancer cells. Material and methods. Two colorectal cancer cell lines SW480 and SW620 were used in the study. Cells treated Hypericin were exposed to visible light. Then cell viability was determined by the MTT assay with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium. Assays were performed for control samples without hypericin and light exposure, with Hyp without light exposure, without Hyp and irradiated with light, and test samples with Hyp and light exposure. Results. In the experiment we reveal, that Hyp- photodynamic activity does not influence the secretion of cytokines. Conclusion. The obtaining results confirming the destructive effect of Hyp- PDT on the colon cancer cells, show a possibility of extending the indication for photodynamic therapy using Hyp, qualification of precancerous changes.

Effectiveness of photodynamic therapy (PDT) in the management of symptomatic oral lichen planus -A systematic review.

Oral Lichen Planus (OLP) is a chronic mucocutaneous inflammatory disease of unknown aetiology characterized by T cell mediated autoimmune response which trigger apoptosis of basal cells of an oral epithelium. Corticosteroids are the primary therapeutic option for symptomatic OLP however treatment of lesions unresponsive to corticosteroids that tend to recur are becoming challenging for the clinicians. Currently photodynamic therapy (PDT) is being explored as a new curative option for reduction of pain and/or burning sensation associated with OLP lesions. The aim of this systematic review was to analyse studies from literature on the therapeutic effectiveness of PDT in management of symptomatic OLP unresponsive to corticosteroid therapy. The electronic retrieval systems and databases PUBMED [MEDLINE], EMBASE, SCOPUS, WEB OF SCIENCE, GOOGLE SCHOLAR, and SCIENCE DIRECT were searched independently by two authors for relevant articles from January 2015 till July 2021. Primary studies focussed on the role of PDT in treatment of symptomatic OLP and published in English were included. Out of the 370 articles, only ten studies met the selection criteria. Included studies demonstrated PDT as an effective alternative modality to treat symptomatic OLP with no drop outs. In all studies, with PDT reduction in lesion size and VAS score was observed during each follow up sessions and after treatment (approx. 12 weeks) when compared to pre-treatment level (p<0.001). Four studies noted PDT to be more effective than topical corticosteroids in reduction of signs and symptoms of OLP (p=0.001). In the future, long-term studies on larger population should be conducted to establish the clinical effectiveness in PDT in symptomatic OLP. Studies should take into consideration different sources of light and photosensitizers to determine the ideal parameters of PDT treatment for OLP. Wavelength is the most important factor in all types of photo therapies, so the most appropriate wavelength should be selected to obtain better outcome.

Hybrid Quantum Dot as Promising Tools for Theranostic Application in Cancer

Cancer is one of the leading causes of death worldwide. In the last few decades, cancer treatment has come a long way, but multidrug resistance (MDR) in cancer still has low survival rates. It means that much research is required for an accurate diagnosis and effective therapy. The new era of cancer research could include theranostic approaches and targeted delivery of chemotherapeutic agents utilizing the nanoparticulate system. Recently, there has been much interest gained among researchers for carbon-based and graphene-based quantum dots due to their higher biocompatibility and ease of biofunctionalization compared to conventional heavy metal quantum dots. Moreover, these quantum dots have various interesting utilities, including bioimaging, biosensing, quantum dots-mediated drug delivery, and their role in photodynamic therapy (PDT) and photothermal therapy (PTT). The current review highlighted the utility of hybrid quantum dots as a theranostic system in different cancers and discussed the various bio-molecules conjugated hybrid quantum dots investigated for diagnostic/therapeutic applications in cancer. The influence of conjugation of different biomolecules, such as folic acid, PEG, etc., with hybrid quantum dots on their biopharmaceutical attributes (such as aqueous solubility, tumor penetrability, stability of loaded therapeutics in the tumor microenvironment), delivery of drugs specifically to tumor tissues, and its therapeutic outcome in different cancer has also been discussed.

Macrophage-targeted nanoparticles mediate synergistic photodynamic therapy and immunotherapy of tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that poses a serious global public health threat. Due to the high incidence of adverse reactions associated with conventional treatment regimens, there is an urgent need for better alternative therapies. CpG oligodeoxynucleotides (CpG ODNs) are synthetic oligodeoxyribonucleotide sequences. They can induce a Th1-type immune response by stimulating Toll-like receptors (TLRs) in mammalian immune cells, thus killing Mtb. However, due to the negative charge and easy degradation of CpG ODNs, it is necessary to deliver them into cells using nanomaterials. PCN-224 (hereinafter referred to as PCN), as a metal-organic framework based on zirconium ions and porphyrin ligands, not only has the advantage of high drug loading capacity, but also the porphyrin molecule in it is a type of photosensitizer, which allows these nanocomposites to play a role in photodynamic therapy (PDT) while delivering CpG ODNs. In addition, since Mtb mainly exists in macrophages, targeting anti-TB agents to macrophages is helpful to improve the anti-TB effect. Phosphatidylserine (PS) is a biological membrane phospholipid that is normally found on the inner side of cell membranes in, for example, plant and mammalian cells. When apoptosis occurs, PS can flip from the inner side of the cell membrane to the surface of the cell membrane, displaying a specific "eat-me" signal that can be recognized by specific receptors on macrophages. Therefore, we can use this macrophage-targeting property of PS to construct bio-inspired targeted drug delivery systems. In this study, we constructed PCN-CpG@PS nanocomposites. PCN-CpG@PS, combining PDT and immunotherapy, is designed to target macrophages at the site of a lesion and kill latent Mtb. We physically characterized the nanocomposites and validated their bactericidal ability in vitro and their ability to stimulate the immune system in vivo. The results demonstrated that the targeted nanocomposites have certain in vitro antituberculosis efficacy with good safety.

Liposomes loaded with dual clinical photosensitizers for enhanced photodynamic therapy of cervical cancer.

Photodynamic therapy (PDT) has become a potential anti-cancer strategy owing to its negligible invasiveness, low toxicity, and high selectivity. The photosensitizer (PS) plays an indispensable role in PDT. Herein, a novel type of PS (Ce6-MB@Lips) which can be excited by a near-infrared (NIR) laser was designed and synthesized. Methylene blue (MB) and Chlorin e6 (Ce6), two organic dyes approved by the Food and Drug Administration (FDA), were used to prepare Ce6-MB@Lips by thin-film dispersion method, which improve the water solubility of Ce6 and reduce the cytotoxicity of MB. The Ce6-MB@Lips were shown to have a spherical nanostructure with an average particle size of 160.3 nm and excellent water solubility. Then the optical properties of Ce6-MB@Lips were further studied. Ce6-MB@Lips showed absorption peaks at 413 nm/670 nm and fluorescence peak at 697 nm. Compared with Ce6@Lips and MB@Lips, Ce6-MB@Lips showed better stability, stronger fluorescence intensity, and higher singlet oxygen (1O2) generation ability. Cell experimental analysis exhibited that the stable Ce6-MB@Lips showed low cytotoxicity, high phototoxicity and high reactive oxygen species (ROS) production capacity. After effective cell internalization, the prepared Ce6-MB@Lips showed excellent ability to promote tumor cell apoptosis in vitro. The Ce6-MB@Lips could be a promising candidate for PDT of cervical cancer.

Iridium and Ruthenium Complexes Bearing Perylene Ligands.

The present review summarizes the work carried out mostly in the last decade on iridium and ruthenium complexes bearing various perylene ligands, of particular interest for bioimaging, photodynamic therapy, and solar energy conversion. In these complexes, the absorption spectra and the electrochemical properties are those of the perylene subunit plus those of the metal moiety. In contrast, the emissions are completely changed with respect to perylenes considered alone. Thus, fully organic perylenes are characterized by a strong fluorescence in the visible region, lifetimes of a few nanoseconds, and luminescence quantum yields approaching 100%, whereas perylene Ir and Ru complexes usually do not emit; however, in few cases, weak phosphorescent emissions, with lifetimes in the range of microseconds and relatively low quantum yields, are reported. This is due to a strong interaction between the perylene core and the heavy metal center, taking place after the excitation. Nevertheless, an important advantage deriving from the presence of the heavy metal center is represented by the ability to generate large amounts of singlet oxygen, which plays a key role in photodynamic therapy.

Photochemical Targeting of Mitochondria to Overcome Chemoresistance in Ovarian Cancer †.

Ovarian cancer is the most lethal gynecologic malignancy with a stubborn mortality rate of ~65%. The persistent failure of multiline chemotherapy, and significant tumor heterogeneity, has made it challenging to improve outcomes. A target of increasing interest is the mitochondrion because of its essential role in critical cellular functions, and the significance of metabolic adaptation in chemoresistance. This review describes mitochondrial processes, including metabolic reprogramming, mitochondrial transfer and mitochondrial dynamics in ovarian cancer progression and chemoresistance. The effect of malignant ascites, or excess peritoneal fluid, on mitochondrial function is discussed. The role of photodynamic therapy (PDT) in overcoming mitochondria-mediated resistance is presented. PDT, a photochemistry-based modality, involves the light-based activation of a photosensitizer leading to the production of short-lived reactive molecular species and spatiotemporally confined photodamage to nearby organelles and biological targets. The consequential effects range from subcytotoxic priming of target cells for increased sensitivity to subsequent treatments, such as chemotherapy, to direct cell killing. This review discusses how PDT-based approaches can address key limitations of current treatments. Specifically, an overview of the mechanisms by which PDT alters mitochondrial function, and a summary of preclinical advancements and clinical PDT experience in ovarian cancer are provided.

The water effect on the spectral properties of porphyrin sensitizers

Porphyrin derivatives, which played a key role in photodynamic therapy (PDT), exhibit different photophysical and photochemical properties in aqueous solution of organism and organic solvents. Limited by the poor water-soluble, present studies on porphyrin derivatives covered the real performance in aqueous solution of organism. In this study, the water effect on the properties of porphyrin derivatives was investigated by the water proportion evolution spectroscopy. The variation in fluorescence intensities of hematoporphyrin monomethyl ether (HMME) in solvents with different proportions of methanol and water were analyzed. Corresponding absorption spectra were measured, and the absorption intensity at the excitation wavelength is found to be unchanged. Utilizing Perrin-Jablonski energy level structure, as well as related rate equations, the fluorescence variation is supposed to be origin from both the decreased intersystem crossing rate (kISC) and increased non-fluorescence transition rate (knF). The decrease of kISC is induced by the raise of the lowest vibrational energy level of the first singlet excited state (S1), which can be verified by the blue-shift of the absorption and fluorescence spectra. The increase of the knF was caused by the high-energy vibrations in aqueous solutions. The fluorescence lifetimes are also measured, which consist with our analysis. Our research not only uncovered the water effect on the properties of HMME, but also provided a way to insight the PDT behavior of porphyrin derivatives in the aqueous solution of organism.

The Role of Photodynamic Therapy in Triggering Cell Death and Facilitating Antitumor Immunology.

Cancer is a major threat to human health because of its high mortality, easy recurrence, strong invasion, and metastasis. Photodynamic therapy (PDT) is a promising minimally invasive treatment for tumor. Compared with traditional treatment methods, PDT is less invasive and does not easily damage normal tissues. Most of the effects of this treatment are due to the direct effects of singlet oxygen together with reactive oxygen species. PDT can provide the source of active oxygen for the Fenton reaction, which enhances ferroptosis and also improves the efficacy of PDT in antitumor therapy. Additionally, in contrast to chemotherapy and radiotherapy, PDT has the effect of stimulating the immune response, which can effectively induce immunogenic cell death (ICD) and stimulate immunity. PDT is an ideal minimally invasive treatment method for tumors. In this paper, according to the characteristics of anti-tumor immunity of PDT, some tumor treatment strategies of PDT combined with anti-tumor immunotherapy are reviewed.

Chemical Probes and Activity-Based Protein Profiling for Cancer Research.

Chemical probes can be used to understand the complex biological nature of diseases. Due to the diversity of cancer types and dynamic regulatory pathways involved in the disease, there is a need to identify signaling pathways and associated proteins or enzymes that are traceable or detectable in tests for cancer diagnosis and treatment. Currently, fluorogenic chemical probes are widely used to detect cancer-associated proteins and their binding partners. These probes are also applicable in photodynamic therapy to determine drug efficacy and monitor regulating factors. In this review, we discuss the synthesis of chemical probes for different cancer types from 2016 to the present time and their application in monitoring the activity of transferases, hydrolases, deacetylases, oxidoreductases, and immune cells. Moreover, we elaborate on their potential roles in photodynamic therapy.

NANO-ANTIMICROBIALS IN ENDODONTICS

A root canal system exhibits a challenging environmental condition about the availability of nutrients and oxygen. Usually, chemical antimicrobials (topical) are used within the root canals in combination with mechanical instrumentation to achieve microbe-free root canals before obturating the root canal with an inert filling material. Antimicrobial resistance (AMR) has emerged as one of the primary public health problems of the 21st century. It threatens the effective prevention and treatment of an ever-increasing range of infections caused by bacteria, viruses, parasites, and fungi which is no longer susceptible to the currently used antibiotics. One of the important requirements of endodontic treatment is the ability to eliminate microorganisms from the root canal system and prevent re-entry of microbes. This antimicrobial effect is achieved by a combination of chemical and mechanical disinfection. Due to increasing antimicrobial resistance, the efficacy of traditionally used irrigants has been decreased. Owing to the limitation of currently used antibiotics it paves way for nano antimicrobial-based irrigants.It has been emphasized that the addition of antibacterial nanoparticles in root canal sealers would upsurge the direct (based on the direct antibacterial assay) and diffusible antibacterial effects (based on a membrane-restricted antibacterial assay) of the root canal sealers. Additionally, nanoparticles when incorporated into intracanal medicament have shown added benefits.Nanoparticle-based photosensitizers have been considered to potentiate the antimicrobial efficacy of photodynamic therapy (PDT). The antibacterial nanoparticle-based treatment has the potential to improve antibacterial/ antibiofilm efficacy. They have distinct advantages when applied in endodontics. The whole concept of nanotechnology in health care should be accepted with positive zeal for future development. This review paper describes the scope of nano antimicrobials in endodontics as irrigants, intracanal medicaments, and their role in photodynamic therapy, sealers, and obturating materials.

Role of Photodynamic Therapy in Non-Surgical Periodontal Treatment

Role of Photodynamic Therapy in Non-Surgical Periodontal Treatment

Advances in Management of Bladder Cancer-The Role of Photodynamic Therapy.

Photodynamic therapy (PDT) is a non-invasive and modern form of therapy. It is used in the treatment of non-oncological diseases and more and more often in the treatment of various types of neoplasms in various locations including bladder cancer. The PDT method consists of local or systemic application of a photosensitizer, i.e., a photosensitive compound that accumulates in pathological tissue. Light of appropriate wavelength is absorbed by the photosensitizer molecules, which in turn transfers energy to oxygen or initiates radical processes that leads to selective destruction of diseased cells. The technique enables the selective destruction of malignant cells, as the photocytotoxicity reactions induced by the photosensitizer take place strictly within the pathological tissue. PDT is known to be well tolerated in a clinical setting in patients. In cited papers herein no new safety issues were identified. The development of anti-cancer PDT therapies has greatly accelerated over the last decade. There was no evidence of increased or cumulative toxic effects with each PDT treatment. Many modifications have been made to enhance the effects. Clinically, bladder cancer remains one of the deadliest urological diseases of the urinary system. The subject of this review is the anti-cancer use of PDT, its benefits and possible modifications that may lead to more effective treatments for bladder cancer. Bladder cancer, if localized, would seem to be a good candidate for PDT therapy since this does not involve the toxicity of systemic chemotherapy and can spare normal tissues from damage if properly carried out. It is clear that PDT deserves more investment in clinical research, especially for plant-based photosensitizers. Natural PS isolated from plants and other biological sources can be considered a green approach to PDT in cancer therapy. Currently, PDT is widely used in the treatment of skin cancer, but numerous studies show the advantages of related therapeutic strategies that can help eliminate various types of cancer, including bladder cancer. PDT for bladder cancer in which photosensitizer is locally activated and generates cytotoxic reactive oxygen species and causing cell death, is a modern treatment. Moreover, PDT is an innovative technique in oncologic urology.

Role of Photo Dynamic Therapy as an adjunct in periodontal therapy

Role of Photo Dynamic Therapy as an adjunct in periodontal therapy

Highly Efficient Multifunctional Organic Photosensitizer with Aggregation-Induced Emission for In Vivo Bioimaging and Photodynamic Therapy.

Photosensitizers play a critical role in photodynamic therapy (PDT). Multifunctional organic nanoparticles (NPs) that possess bright fluorescence in aggregates, high singlet oxygen (1O2) quantum yield, near-infrared (NIR) absorption and emission, large Stokes shift, two-photon bioimaging, specific organelle targeting, high PDT efficiency, as well as good biocompatibility and photostability are ideal candidate photosensitizers for image-guided PDT. Due to its enhanced fluorescence and high 1O2 generation efficiency in aggregate states, photosensitizers with aggregation-induced emission (AIE) characteristics have attracted increasing interest in PDT. In this study, a new AIE-active Schiff base 5-(((5-(7-(4-(diphenylamino)phenyl)benzo[c][1,2,5]thiadiazol-4-yl)thiophen-2-yl)methylene)amino)-3-methylthiophene-2,4-dicarbonitrile (TBTDC) based on a D-A-π-A skeleton has been designed and synthesized, and it can be readily encapsulated by Pluronic F-127 to form uniform nanoparticles. TBTDC NPs exhibit bright NIR emission at 825 nm with a Stokes shift up to 300 nm, impressive two-photon bioimaging capability with tissue penetration deep into 300 μm, high 1O2 generation quantum yield (0.552), specific targeting to lysosome, as well as good biocompatibility and photostability. Furthermore, TBTDC NPs present remarkable cytotoxicity for tumor cells and suppression of tumor growth in nude mice through reactive oxygen species generation upon white light irradiation. These results reveal that TBTDC NPs have great potential to become excellent candidates for multifunctional organic photosensitizers for two-photon bioimaging and image-guided PDT and are promising in future clinical applications.

The Contemporary Role of Photodynamic Therapy in the Treatment of Pachychoroid Diseases.

Recent advances in retinal imaging technology have improved our understanding in the pathogenesis and evolvement of various chorioretinal diseases. Central serous chorioretinopathy and polypoidal choroidal vasculopathy are now recognized to belong to the same spectrum of disorders known as pachychoroid diseases. Pachychoroid diseases have similar pathogenesis pathway and common characteristics of thickened choroid, dilated outer choroidal vessels, and thinning of choriocapillaris. More disease entities have been identified to belong to this disease spectrum. Photodynamic therapy can induce choroidal hypoperfusion, remodeling of abnormal choroidal vessels, and reduction of choroidal congestion. It is known to be an effective treatment for chronic central serous chorioretinopathy and polypoidal choroidal vasculopathy. Many new studies are being performed to investigate its efficacy in other pachychoroid diseases. In this review, we provided an overview of the rationale, efficacy, and treatment strategies of photodynamic therapy in different pachychoroid diseases and discussed its role in the management along with other treatment modalities with most updated clinical evidence.

Photodynamic Therapy Using Toluidine Blue O (TBO) Dye as a Photosensitizer against Leishmania major.

Background:Photodynamic therapy (PDT) is alternative treatment of cutaneous leishmaniasis (CL), and phenolthiazine dyes such as Toluidine Blue O (TBO) have the potential role in PDT and notably affect parasites inactivation. This study aimed to evaluate the effectiveness of PDT by using TBO and a light-emitting diode (LED) in the treatment of zoonotic CL (ZCL).Methods:The study was conducted in Iran University of Medical Sciences, Tehran, Iran in 2018–2020. Different concentration (7.8 μg/mL up to 500 μg/mL) of TBO as a photosensitizer and a 630 nm LED light as a source of light were used for antileishmanial activity against both forms of Leishmania major promastigotes and intracellular amastigotes. Effective concentration (EC50) and cell cytotoxicity (CC50) were calculated in both infected and non-infected J774.A1 macrophages, respectively. As well as inhibitory concentration (IC50) was quantified in L. major promastigotes for 2 h, 24 h, and 48 h after incubation using a MTT colorimetric assay.Results:TBO dye in combination with the PDT significantly decreases the L. major promastigotes and intra-cellular amastigotes viability when compared with TBO alone. Both TBO dye in combination with the PDT and TBO alone had no toxic effects on the mice macrophages; however, it significantly killed the entered parasites inside the cells. Our results in the current study established satisfactory findings in clearing intracellular L. major parasites in in-vitro conditions.Conclusion:TBO dye in combination with the PDT can be considered as a harmless, effective and importantly perfect treatment against L. major, causative agent of ZCL, in an in-vitro situation without any negative toxicity to the mice macrophages.