Photodynamic Therapy Research Research Articles

Light exposure of tetra-cationic porphyrins containing peripheral Pd(II)-bipyridyl complexes and the induced effects on purified DNA molecule, fibroblast and melanoma cell lines.

Photodynamic therapy (PDT) combines a light source, oxygen, and a photosensitizer (PS) to generate reactive oxygen species (ROS) for treating diseases. In this study, we evaluated two meso-tetra-pyridyl porphyrins with [Pd(bpy)Cl]+, namely 3-PdTPyP and 4-PdTPyP, as PS for PDT application. DNA interaction was assessed by spectroscopic measurements (UV-Vis and fluorescence emission), viscosity analysis, and molecular docking simulations. The results indicate that Pd(II)-porphyrins do not intercalate into DNA, suggesting that the minor groove is the primary interaction site, mainly through van der Waals forces. These metalloporphyrins effectively induced nitrogenous bases oxidation, particularly in purines, after white light irradiation. The induced DNA lesions were able to inactivate plasmid DNA metabolism (DNA replication and transcription) in a bacterial model. 3-PdTPyP and 4-PdTPyP significantly decreased the viability of treated melanoma cell lines (A375 and B16-F10), demonstrating that melanoma cell lines were more sensitive to these Pd(II)-porphyrins than the fibroblast cell line (L929). Moreover, 3-PdTPyP was more photototoxic to A375 cells (IC50 = 0.43 μM), whereas 4-PdTPyP was more photototoxic to B16-F10 cells (IC50 = 0.51 μM). These findings suggest that these porphyrins are promising PS for future PDT research focused on skin cancer.

A Systemic Review on Photodynamic Therapy: Emerging Technology with Healing Process

Abstract: Photodynamic therapy (PDT) is a non-invasive treatment of cancer patients who take a photosensitizer and expose their tumours to light after administering it topically or intravenously. Understanding apoptosis under oxidative conditions makes PDT a more effective treatment. Tissue oxygen, tumour-selective photosensitizer dyes, and customised lighting are needed to create fatal reactive oxygen species (ROS) in cancer. PDT has decreased morbidity and improved survival and status of life when used in combination with other treatments, especially in early-stage malignant tumours. Using interstitial light delivery, PDT can cure large, hidden tumours that would otherwise necessitate extensive surgery. This overview describes the foundational historical work that has shaped the technique since the early 1900s. PDT's efficacy is also increased by innovative photosensitizers and tweaks that increase tumour selectivity. Adverse effects and treatment during therapy, as well as innovative PDT-based applications, are explored in this review. Finally, PDT research gaps and clinical trials have been identified as potential issues.

Bibliometric and visual analysis of photodynamic therapy for lung cancer from 2010 to 2022.

A growing body of research shows that photodynamic therapy (PDT) has become an important mode of treatment in the field of lung cancer (LC) in recent years. Although numerous papers related to PDT in LC have been published, no bibliometric studies have been conducted to summarize the research prospects and highlight the research trends and hotspots in this field. This bibliometric analysis was conducted to investigate and provide a systematic understanding of the development of PDT research for LC over the past 13 years with the aim of providing a reference for new directions and strategies in the field of PDT for LC. In May 2023, relevant publications from the Web of Science Core Collection were downloaded, and CiteSpace and VOSviewer were used to conduct the scientometrics analysis in this study.Results: A total of 2,932 articles and reviews that met the inclusion criteria were retrieved, with China dominated the volume of publications from 2010 to 2022 and the most prolific institution was Shanghai Jiao Tong University. PDT can be utilized for the diagnosis and treat LC. Bronchoscopic fluorescence diagnosis using photosensitizers helps to detect tumor changes in the large bronchial mucosa. In the future, we should actively explore the use of new photosensitizers, including the development of nanomaterials, in addition, PDT combined with other treatments can significantly prolong survival. This combination therapy may also be the direction of future research.

Recent Studies in Photodynamic Therapy for Cancer Treatment: From Basic Research to Clinical Trials.

Photodynamic therapy (PDT) is an emerging and less invasive treatment modality for various types of cancer. This review provides an overview of recent trends in PDT research, ranging from basic research to ongoing clinical trials, focusing on different cancer types. Lung cancer, head and neck cancer, non-melanoma skin cancer, prostate cancer, and breast cancer are discussed in this context. In lung cancer, porfimer sodium, chlorin e6, and verteporfin have shown promising results in preclinical studies and clinical trials. For head and neck cancer, PDT has demonstrated effectiveness as an adjuvant treatment after surgery. PDT with temoporfin, redaporfin, photochlor, and IR700 shows potential in early stage larynx cancer and recurrent head and neck carcinoma. Non-melanoma skin cancer has been effectively treated with PDT using methyl aminolevulinate and 5-aminolevulinic acid. In prostate cancer and breast cancer, PDT research is focused on developing targeted photosensitizers to improve tumor-specific uptake and treatment response. In conclusion, PDT continues to evolve as a promising cancer treatment strategy, with ongoing research spanning from fundamental investigations to clinical trials, exploring various photosensitizers and treatment combinations. This review sheds light on the recent advancements in PDT for cancer therapy and highlights its potential for personalized and targeted treatments.

A monoamine oxidase-A inhibitor phthalocyanine conjugate for targeted photodynamic therapy and inhibition of prostate cancer metastasis in vitro

Photodynamic therapy (PDT), as an alternative non-invasive clinical treatment modality, has been extensively employed for various anticancer applications in preclinical and clinical trials. However, there is hardly any PDT research based on invasive or metastatic tumors. But it can't be ignored that cancer metastases are responsible for 90% of all cancer-related death. Among these metastatic cancers, prostate cancer (PCa) is regarded as one of the leading causes of cancer related deaths amongst male patients due to its high metastasis and high fatality rate. At present, it remains a great challenge to apply traditional PDT technology for inhibiting prostate cancer metastasis. In this work, we successfully designed and synthesized a novel MAO-A targeted photosensitizer Pc-MLB for targeted photodynamic treatment of prostate cancer and inhibiting its metastasis in vitro. In vitro experiments demonstrate that Pc-MLB shows high target affinity and specificity towards prostate cancer cells and remarkable photodynamic anticancer activity compared with the control. More significantly, the migration and invasion assays show that Pc-MLB exhibits the ability to inhibit the migration and metastasis of prostate cancer cells to some extent.

Critical PDT theory II: Current concepts and indications

While photodynamic therapy (PDT) is effective for the eradication of select neoplasia and certain other pathologic conditions, it has yet to achieve wide acceptance in clinical medicine. A variety of factors contribute to this situation including relations with the pharmaceutical industry that have often been problematic. Some current studies relating to photodynamic effects are ‘phenomenological’, i.e., they describe phenomena that only reiterate what is already known. The net result has been a tendency of granting agencies to become disillusioned with support for PDT research. This report is intended to provide some thoughts on current research efforts that improve clinical relevance and those that do not.

Microtumor Models as a Preclinical Investigational Platform for Photodynamic Therapy.

Classic preclinical investigations on the mechanisms and effects of photodynamic therapy (PDT) are typically performed in two-dimensional cell cultures that have some, albeit limited, relevance to cancer biology. Bioengineered three-dimensional (3D) culture models of cancer are gaining traction in translational oncology as microtumors recapitulate the tumor architectures and cellular heterogeneity more faithfully than conventional 2D cultures. These 3D models bridge a gap between highly relevant but low-throughput in vivo animal models and high-throughput two-dimensional cultures with low clinical relevance, and thus hold promise as preclinical testing platforms in PDT research. Here, we discuss the potential applications of organotypic cancer models for PDT research and provide two well-established methodologies for generating 3D cultures of cancer: a liquid-suspended spheroid model and an adherent microtumor culture model grown on extracellular matrix scaffolds. Particular emphasis is given to harvesting the cultures for the purpose of immunoblotting and flow cytometry.

Progress and trends of photodynamic therapy: From traditional photosensitizers to AIE-based photosensitizers.

Photodynamic therapy (PDT) is an established clinical treatment technology which utilizes excitation light of a specific wavelength to activate photosensitizers (PSs) to generate reactive oxygen species (ROS), which leads to cancer cell death. Over the past decades of PDT research, progress have been made in the development of PSs. However, many inherent characteristics of traditional PSs have caused various problems in PDT, such as low treatment efficiency at aggregation state and shallow treatment depth. In solution to these problems, aggregation-induced emission (AIE)-based PSs have been reported in recent years. Here, this article reviews the design strategy and the biomedical applications of AIE PSs in detail, which begins with a summary of traditional PSs for a comparison between traditional PSs and AIE PSs. Subsequently, the different functional AIE PSs in photodynamic cancer cells ablation and image-guided therapy are discussed in detail taking controllable excitation wavelength, stimulus response and PDT/photothermal therapy synergistic effect as examples. These studies have demonstrated the great potential of AIE PSs as effective theranostic agents. And the review provides references for the development of new PSs and hopefully spur research interest in AIE PSs for future clinical application.

Enhanced photodynamic therapy by encapsulation of perfluorocarbon into PEGylated near-infared dyes

Near-Infrared (NIR) dyes, with improved tissue penetration, minimal invasiveness and high specificity, have gained great interests in diagnosing and treating tumors. However, the poor solubility in aqueous medium and low 1O2 quantum yields of NIR dyes restrict their application in PDT (photodynamic therapy) research. Herein, a novel nanosystem with modifying the NIR dyes and encapsulating perfluorocarbon is reported for improving the PDT effectiveness of NIR dyes. By adding the PEG2000-SH and the C13 carbon chain to a NIR representative dye IR780, the new formed material PEG-IR780-C13 shows good solubility in water. Then PFTBA was encapsulated into PEG-IR780-C13 to form a nanosystem (PFTBA@PEG-IR780-C13). When exposed to laser irradiation, the nanosystem showed enhanced production of 1O2 and significantly increased PDT both in vivo and in vitro. Therefore, this work provides an approach for design and application of NIR dyes.

Extracellular Matrix Containing invitro Three-dimensional Tumor Models in Photodynamic Therapy-related Research.

Three-dimensional (3D) tumor models have been intensively evaluated for their use in cancer research, and there is a strong rationale behind using 3D cell cultures in photodynamic therapy (PDT)-related experimentation. In this contribution, it is explained why 3D cell cultures containing extracellular matrix (ECM) are preferred for this purpose. Results of experimental studies utilizing ECM-containing 3D cellular models in PDT research are summarized. Finally, the design of invitro 3D models that would provide clinically relevant information is discussed.

Real-Time Monitoring of Singlet Oxygen and Oxygen Partial Pressure During the Deep Photodynamic Therapy In Vitro.

Photodynamic therapy (PDT) is an effective noninvasive method for the tumor treatment. The major challenge in current PDT research is how to quantitatively evaluate therapy effects. To our best knowledge, this is the first time to combine multi-parameter detection methods in PDT. More specifically, we have developed a set of system, including the high-sensitivity measurement of singlet oxygen, oxygen partial pressure and fluorescence image. In this paper, the detection ability of the system was validated by the different concentrations of carbon quantum dots. Moreover, the correlation between singlet oxygen and oxygen partial pressure with laser irradiation was observed. Then, the system could detect the signal up to 0.5cm tissue depth with 660nm irradiation and 1cm tissue depth with 980nm irradiation by using up-conversion nanoparticles during PDT in vitro. Furthermore, we obtained the relationship among concentration of singlet oxygen, oxygen partial pressure and tumor cell viability under certain conditions. The results indicate that the multi-parameter detection system is a promising asset to evaluate the deep tumor therapy during PDT. Moreover, the system might be potentially used for the further study in biology and molecular imaging.

Developments in PDT Sensitizers for Increased Selectivity and Singlet Oxygen Production.

Photodynamic therapy (PDT) is a minimally-invasive procedure that has been clinically approved for treating certain types of cancers. This procedure takes advantage of the cytotoxic activity of singlet oxygen (1O2) and other reactive oxygen species (ROS) produced by visible and NIR light irradiation of dye sensitizers following their accumulation in malignant cells. The main two concerns associated with certain clinically-used PDT sensitizers that have been influencing research in this arena are low selectivity toward malignant cells and low levels of 1O2 production in aqueous media. Solving the selectivity issue would compensate for photosensitizer concerns such as dark toxicity and aggregation in aqueous media. One main approach to enhancing dye selectivity involves taking advantage of key methods used in pharmaceutical drug delivery. This approach lies at the heart of the recent developments in PDT research and is a point of emphasis in the present review. Of particular interest has been the development of polymeric micelles as nanoparticles for delivering hydrophobic (lipophilic) and amphiphilic photosensitizers to the target cells. This review also covers methods employed to increase 1O2 production efficiency, including the design of two-photon absorbing sensitizers and triplet forming cyclometalated Ir(III) complexes.

Photodynamic therapy: Truly a marriage between a drug and a light

Microbial biofilms in the oral cavity are involved in the etiology of various oral conditions, including caries, periodontal and endodontic diseases, oral malodor, denture stomatitis, candidiasis and dental implant failures. It is generally recognized that the growth of bacteria in biofilms imparts a substantial decrease in susceptibility to antimicrobial agents compared with cultures grown in suspension. It is therefore not surprising that bacteria growing in dental plaque, a naturally occurring biofilm, show increased resistance to antimicrobial agents. As result there is pronounced interest and keenness in the development of alternate antimicrobial concepts. Therefore, the application of alternative method to eradicate bacteria from periodontal pockets is desirable. One such approach is photodynamic therapy (PDT). The purpose of this review was to evaluate the effectiveness of PDT for periodontitis as an adjunct to non-surgical treatment of scaling and root planning. This review provides an overview of PDT with emphasis on its current status as an antimicrobial therapy to control oral bacteria. Finally, new frontiers of antimicrobial PDT research will be introduced, including targeting strategies that may open new opportunities for the maintenance of bacterial homeostasis in dental plaque, thereby providing the opportunity for more effective disease prevention and control. Thus, the available knowledge of PDT should encourage a more clinically oriented application of this technique.

Abstract 3923: Photoacoustic image guided photodynamic therapy of glioblastoma.

Abstract Introduction: Glioblastoma multiforme(GBM) is an aggressive cancer with bleak survival rates and limited new treatment options. Fluorescence guided resection of GBM followed by photodynamic therapy (PDT) has shown promise in several chemo-or radiotherapy non-responsive GBM treatments clinically. PDT causes cytotoxicity with a combination of specific wavelength of light and photosensitizer (PS). Fluorescence is used in PDT research for detection of tumors, as the PS is also fluorescent. However, typically these molecules have low fluorescence quantum yields but good singlet oxygen yields to cause photodynamic damage. Also, in-vivo florescence images are surface-weighted and donot provide 3D image of the tumoral drug accumulation. In this study we utilize photoacoustic imaging (PA), a non-invasive, non-ionizing technique that provides contrast based on optical absorption properties of the tissue, to obtain 3D biodistribution of different fluorophores and PDT agents such as methylene blue (MB) free or encapsulated in liposomes in orthotopic brain tumors. We encapsulated verteporfin and MB in liposomes to increase its circulation half-life in-vivo and tumoral accumulation due to the enhanced-permeation and retention effect. Moreover, PA imaging can also be used to monitor tumoral blood oxygen saturation and this information is critical in PDT as oxygen plays a major role in creation of singlet oxygen cytotoxic species. Methods and Results: In this study, U87 glioma cells and patient derived GBM6 glioma cells were implanted orthotopically in the brain in 4-6 weeks old nude mice. 10 days post implantation, a burr hole was made in the skull to image intravenously injected liposomal methylene blue (10 mg/kg) uptake in the tumor. The liposomes were ∼110 nm in diameter evaluated using dynamic light scattering. A methylene blue loading efficiency of ∼50% was obtained in these liposomes. We observed that 2 hours post I.V. injection, the photoacoustic signal in brain tumor region increased ∼2.3 times and remained the same in non-tumor regions within the brain. We performed pilot studies in orthotopic glioma models that demonstrated: i) the efficacy of the photosensitizer encapsulated liposomes to accumulate in the glioma tumors, ii) ability of PA imaging technique to monitor the 3D heterogeneous uptake of the liposome constructs and iii) monitor PDT-induced changes in tumor vascular oxygen saturation non-invasively in real time. Conclusions: Taken together, we anticipate significant tumor burden reduction in our on-going in-vivo studies where the PDT light dose will be compensated based on the photoacoustic image information of the PDT agents uptake in the tumor. The findings of this study will form the basis for customized photodynamic therapy for glioblastoma and have the potential to serve as a platform for treatment of other cancers. Citation Format: Srivalleesha Mallidi, Huang-Chiao Huang, Joyce Y. Liu, Lawrence Mensah, Zhiming Mai, Tayyaba Hasan. Photoacoustic image guided photodynamic therapy of glioblastoma. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3923. doi:10.1158/1538-7445.AM2013-3923

Why Not Introducing the Third Dimension in Photodynamic Therapy Research?

Photodynamic therapy (PDT) is a clinically approved procedure for the treatment of diseases characterized by uncontrolled cell proliferation, particularly cancer. It involves the administration of a photosensitizer (PS) that is able to produce reactive oxygen species (ROS) upon irradiation with light, leading to the selective killing of neoplastic cells. A major challenge in PDT is the development of new PSs and drug-delivery systems that improve therapy efficacy and selectivity. To succeed in drug screening, it is crucial to use cellular systems that precisely reproduce the phenotype of the target tissue in order to obtain reliable biomedical data that correlate with in vivo tests. In this way, three-dimensional (3D) cultures are particularly attractive since they integrate chemical and mechanical signals that arise from extracellular matrix (ECM) and adjacent cells. Importantly, 3D models can mimic in vivo gene expression pattern and molecular gradients. These features significantly affect the outcome of PDT, enhancing the predictive power of 3D models. Therefore, PDT research should rely on the exploitation of this third dimension, guaranteeing a custom-tailor design depending on the tissue to be modeled, an easy applicability and reproducibility. The review summarizes progress in this emerging area.

New Applications of Photodynamic Therapy in Biomedicine and Biotechnology

1 Laboratory of Photodynamic Inactivation of Microorganisms, Department of Materials Science and Physics, University of Salzburg, Hellbrunnerstrase 34, 5020 Salzburg, Austria 2 Department of Dermatology, Eberhard Karls University, Liebermeisterstrase 25, 72076 Tuebingen, Germany 3Department of Internal Medicine I, Paracelsus Medical University and Salzburger Landeskliniken (SALK), Muellner Hauptstrasse 48, 5020 Salzburg, Austria 4 Institute of Physiology and Pathophysiology, Paracelsus Medical University, Strubergasse 21, 5020 Salzburg, Austria 5 Department of Dermatology, University Hospital Regensburg, Franz-Josef-Strauss-Allee 11, 93053 Regensburg, Germany

Modelling fluorescence in clinical photodynamic therapy

Understanding the interactions of non-ionizing radiation with living organisms has been the focus of much research over recent decades. The complex nature of these interactions warrants development of theoretical and experimental studies to gain an insight into predicting and monitoring the success of photodynamic therapy (PDT) protocols. There is a major impetus towards evidence-based recommendations for patient diagnosis, treatment and management. Knowledge of the biophysical aspects of PDT is important for improving dosimetry protocols. Fluorescence in clinical PDT may be used to detect and diagnose pre-malignant and malignant conditions, while photobleaching can monitor changes in fluorescence during treatment. Combining empirical fluorescence photobleaching clinical data with computational modelling enables clinical PDT dosimetry protocols to be investigated with a view to optimising treatment regimes. We will discuss how Monte Carlo radiation transfer (MCRT) modelling has been intercalated in the field of fluorescence detection and PDT. In this paper we highlight important aspects of basic research in PDT by reporting on the current utilisation of fluorescence in clinical PDT from both a clinical and theoretical perspective. Understanding and knowledge of light propagation in biological tissue from these perspectives should have a positive impact on treatment planning.

The role of photodynamic therapy (PDT) physics

Photodynamic therapy (PDT) is an emerging treatment modality that employs the photochemical interaction of three components: light, photosensitizer, and oxygen. Tremendous progress has been made in the last 2 decades in new technical development of all components as well as understanding of the biophysical mechanism of PDT. The authors will review the current state of art in PDT research, with an emphasis in PDT physics. They foresee a merge of current separate areas of research in light production and delivery, PDT dosimetry, multimodality imaging, new photosensitizer development, and PDT biology into interdisciplinary combination of two to three areas. Ultimately, they strongly believe that all these categories of research will be linked to develop an integrated model for real-time dosimetry and treatment planning based on biological response.

Spectrofluorometric Determination of Protoporphyrin IX in Cells Using Acridine as Internal Standard

Photodynamic therapy (PDT) has been used for diagnosis and treatment of patients with various malignant tumors, including cancers of the skin, gastrointestinal tract, lung and uterus. Recently, PDT with using 5-aminolevulinic acid (ALA) for cutaneous diseases has been attracted considerable attentions, because skin is easily accessible to light and drugs. Since ALA was used as a pre-drug of the photosensitizer in PDT research by Kenedy et al. in 1990, a number of ALA ester derivatives have been synthesized and applied to PDT. ALA and its ester derivatives are precursors of protoporphyrin IX (PpIX) in the biosynthetic pathway of heme. They are normally biosynthesized in vivo from glycine and succinyl-coenzyme A in mitochondria and then converted into the actual photosensitizer, PpIX. PpIX produced through the heme biosynthetic pathway emits fluorescence strongly and photobleaches rapidly under production of singlet oxygen. The amount of ALA-induced porphyrins can be generally determined by measuring the fluorescence under various experimental conditions. Most papers have reported that the amount of fluorescence was determined by the measurement of fluorescence intensity at the maximum emission wavelength. Fluorescence spectra were measured by single-beam operation in which a sample is examined to determine the amount of light emitted at a given wavelength. Unstable light source and uneven intensities can cause the false peaks in the spectrum. Equally serious is the variation of the sensitivity of the photomultiplier tubes with regard to wavelength. Moreover, the analytical method for the determination of the fluorescence intensity at a particular wavelength is less sensitive than that of fluorescence spectrum area. The aim of this study is to present a highly sensitive and convenient spectrofluorometric method using an internal standard for the determination of the amount of PpIX produced by ALA in the various tumor and normal cells.

Direct Near-infrared Luminescence Detection of Singlet Oxygen Generated by Photodynamic Therapy in Cells In Vitro and Tissues In Vivo¶

Singlet oxygen (1O2) is believed to be the major cytotoxic agent involved in photodynamic therapy (PDT). Measurement of 1O2 near-infrared (NIR) luminescence at 1270 nm in biological environments is confounded by the strongly reduced 1O2 lifetime and probably has never been achieved. We present evidence that this is now possible, using a new NIR-sensitive photomultiplier tube. Time-resolved 1O2 luminescence measurements were made in various solutions of aluminum tetrasulphonated phthalocyanine (AlS4Pc) and Photofrin. Measurements were also performed on suspensions of leukemia cells incubated with AlS4Pc, and a true intracellular component of the 1O2 signal was clearly identified. Time-resolved analysis showed a strongly reduced 1O2 lifetime and an increased photosensitizer triplet-state lifetime in the intracellular component. In vivo measurements were performed on normal skin and liver of Wistar rats sensitized with 50 mg/kg AlS4Pc. In each case, a small but statistically significant spectral peak was observed at 1270 nm. The 1O2 lifetime based on photon count rate measurements at 1270 nm was 0.03–0.18 μs, consistent with published upper limits. We believe that these are the first direct observations of PDT-generated intracellular and in vivo1O2. The detector technology provides a new tool for PDT research and possibly clinical use.