Photodynamic therapy: current role in the treatment of chorioretinal conditions.
Ontology highlight
ABSTRACT:
SUBMITTER: Newman DK
PROVIDER: S-EPMC4763132 | biostudies-literature | 2016 Feb
REPOSITORIES: biostudies-literature
Publications
Photodynamic therapy: current role in the treatment of chorioretinal conditions.
Eye (London, England) 20160108 2
Verteporfin photodynamic therapy (vPDT) is a selective vaso-occlusive treatment that targets choroidal vascular abnormalities. It was initially developed to treat neovascular age-related macular degeneration using the 'standard' vPDT protocol (verteporfin 6 mg/m(2), vPDT laser fluence 50 J/cm(2)). vPDT therapy has subsequently evolved as an important treatment modality for a range of other chorioretinal conditions including choroidal haemangioma, central serous chorioretinopathy, polypoidal chor ...[more]
Similar Datasets
Project description:Photodynamic therapy (PDT) mostly relies on the generation of singlet oxygen, via the excitation of a photosensitizer, so that target tumor cells can be destroyed. PDT can be applied in the settings of several malignant diseases. In fact, the earliest preclinical applications date back to 1900's. Dougherty reported the treatment of skin tumors by PDT in 1978. Several further studies around 1980 demonstrated the effectiveness of PDT. Thus, the technique has attracted the attention of numerous researchers since then. Hematoporphyrin derivative received the FDA approval as a clinical application of PDT in 1995. We have indeed witnessed a considerable progress in the field over the last century. Given the fact that PDT has a favorable adverse event profile and can enhance anti-tumor immune responses as well as demonstrating minimally invasive characteristics, it is disappointing that PDT is not broadly utilized in the clinical setting for the treatment of malignant and/or non-malignant diseases. Several issues still hinder the development of PDT, such as those related with light, tissue oxygenation and inherent properties of the photosensitizers. Various photosensitizers have been designed/synthesized in order to overcome the limitations. In this Review, we provide a general overview of the mechanisms of action in terms of PDT in cancer, including the effects on immune system and vasculature as well as mechanisms related with tumor cell destruction. We will also briefly mention the application of PDT for non-malignant diseases. The current limitations of PDT utilization in cancer will be reviewed, since identifying problems associated with design/synthesis of photosensitizers as well as application of light and tissue oxygenation might pave the way for more effective PDT approaches. Furthermore, novel promising approaches to improve outcome in PDT such as selectivity, bioengineering, subcellular/organelle targeting, etc. will also be discussed in detail, since the potential of pioneering and exceptional approaches that aim to overcome the limitations and reveal the full potential of PDT in terms of clinical translation are undoubtedly exciting. A better understanding of novel concepts in the field (e.g. enhanced, two-stage, fractional PDT) will most likely prove to be very useful for pursuing and improving effective PDT strategies.
| S-EPMC8223074 | biostudies-literature
Project description:Calreticulin is recognized as one of the pivotal damage-associated molecular pattern molecules alerting the host of the presence of distressed cells. In this role, calreticulin becomes exposed on the surface of tumor cells treated by several types of cancer therapy including photodynamic therapy (PDT). The goal of the present study was to examine the potential of externally added calreticulin for augmenting antitumor effect mediated by PDT. Recombinant calreticulin was found to bind to mouse SCCVII tumor cells treated by PDT. Compared to the outcome with PDT alone, cure rates of SCCVII tumors grown in immunocompetent C3H/HeN mice were elevated when calreticulin (0.4?mg/mouse) was injected peritumorally immediately after PDT. Such therapeutic gain with PDT plus calreticulin combination was not obtained with SCCVII tumors growing in immunodeficient NOD-scid mice. In PDT-vaccine protocol, where PDT-treated SCCVII cells are used for vaccination of SCCVII tumor-bearing mice, adding recombinant calreticulin to cells before their injection produced improved therapeutic effect. The expression of calreticulin gene was reduced in PDT-treated cells, while no changes were observed with the expression of this gene in tumor, liver, and spleen tissues in PDT-vaccine-treated mice. These findings reveal that externally added recombinant calreticulin can boost antitumor response elicited by PDT or PDT-generated vaccines, and can thus serve as an effective adjuvant for cancer treatment with PDT and probably other cancer cell stress-inducing modalities.
| S-EPMC4315177 | biostudies-literature
Project description:Photodynamic therapy (PDT) has been used as an anti-tumor treatment method for a long time and photosensitizers (PS) can be used in various types of tumors. Originally, light is an effective tool that has been used in the treatment of diseases for ages. The effects of combination of specific dyes with light illumination was demonstrated at the beginning of 20th century and novel PDT approaches have been developed ever since. Main strategies of current studies are to reduce off-target effects and improve pharmacokinetic properties. Given the high interest and vast literature about the topic, approval of PDT as the first drug/device combination by the FDA should come as no surprise. PDT consists of two stages of treatment, combining light energy with a PS in order to destruct tumor cells after activation by light. In general, PDT has fewer side effects and toxicity than chemotherapy and/or radiotherapy. In addition to the purpose of treatment, several types of PSs can be used for diagnostic purposes for tumors. Such approaches are called photodynamic diagnosis (PDD). In this Review, we provide a general overview of the clinical applications of PDT in cancer, including the diagnostic and therapeutic approaches. Assessment of PDT therapeutic efficacy in the clinic will be discussed, since identifying predictors to determine the response to treatment is crucial. In addition, examples of PDT in various types of tumors will be discussed. Furthermore, combination of PDT with other therapy modalities such as chemotherapy, radiotherapy, surgery and immunotherapy will be emphasized, since such approaches seem to be promising in terms of enhancing effectiveness against tumor. The combination of PDT with other treatments may yield better results than by single treatments. Moreover, the utilization of lower doses in a combination therapy setting may cause less side effects and better results than single therapy. A better understanding of the effectiveness of PDT in a combination setting in the clinic as well as the optimization of such complex multimodal treatments may expand the clinical applications of PDT.
| S-EPMC8365093 | biostudies-literature
Project description:Photodynamic therapy (PDT) has been used for the treatment of nonmalignant and malignant diseases from head to toe. Over the last decade its clinical application has gained increasing acceptance around the world. Pre-clinical studies demonstrate that, in addition to the direct local cytotoxicity and vascular effects, PDT can induce various host immune responses. Recent clinical data also show that improved clinical outcomes are obtained through the combination of PDT and immunomodulation. This review will summarize and discuss recent progress in developing innovative regimen of PDT combined with immunomodulation for the treatment of both nonmalignant and malignant diseases.
| S-EPMC2561284 | biostudies-literature
Project description:Photodynamic therapy (PDT) is a clinically approved cancer therapy, based on a photochemical reaction between a light activatable molecule or photosensitizer, light, and molecular oxygen. When these three harmless components are present together, reactive oxygen species are formed. These can directly damage cells and/or vasculature, and induce inflammatory and immune responses. PDT is a two-stage procedure, which starts with photosensitizer administration followed by a locally directed light exposure, with the aim of confined tumor destruction. Since its regulatory approval, over 30 years ago, PDT has been the subject of numerous studies and has proven to be an effective form of cancer therapy. This review provides an overview of the clinical trials conducted over the last 10 years, illustrating how PDT is applied in the clinic today. Furthermore, examples from ongoing clinical trials and the most recent preclinical studies are presented, to show the directions, in which PDT is headed, in the near and distant future. Despite the clinical success reported, PDT is still currently underutilized in the clinic. We also discuss the factors that hamper the exploration of this effective therapy and what should be changed to render it a more effective and more widely available option for patients.
| S-EPMC5332942 | biostudies-literature
Project description:Accumulating evidence indicates that ATP-binding cassette (ABC) transporter ABCG2 plays a key role in regulating the cellular accumulation of porphyrin derivatives in cancer cells and thereby affects the efficacy of photodynamic therapy and photodynamic diagnosis. The activity of porphyrin efflux can be affected by genetic polymorphisms in the ABCG2 gene. On the other hand, Nrf2, an NF-E2-related transcription factor, has been shown to be involved in oxidative stress-mediated induction of the ABCG2 gene. Since patients have demonstrated individual differences in their response to photodynamic therapy, transcriptional activation and/or genetic polymorphisms of the ABCG2 gene in cancer cells may affect patients' responses to photodynamic therapy. Protein kinase inhibitors, including imatinib mesylate and gefitinib, are suggested to potentially enhance the efficacy of photodynamic therapy by blocking ABCG2-mediated porphyrin efflux from cancer cells. This review article provides an overview on the role of human ABC transporter ABCG2 in photodynamic therapy and photodynamic diagnosis.
| S-EPMC3003952 | biostudies-literature
Project description:This review article is based on specifically targeted nanoparticles that have been used in the treatment of melanoma. According to the Skin Cancer Foundation, within 2017 an estimated 9730 people will die due to invasive melanoma. Conventional treatments for nonmalignant melanoma include surgery, chemotherapy, and radiation. For the treatment of metastatic melanoma, 3 therapeutic agents have been approved by the Food and Drug Administration: dacarbazine, recombinant interferon ?-2b, and high-dose interleukin 2. Photodynamic therapy is an alternative therapy that activates a photosensitizer at a specific wavelength forming reactive oxygen species which in turn induces cell death; it is noninvasive with far less side effects when compared to conventional treatments. Nanoparticles are generally conjugated to photosynthetic drugs, since they are biocompatible, stabile, and durable, as well as have a high loading capacity, which improve either passive or active photosensitizer drug delivery to targeted cells. Therefore, various photosynthetic drugs and nanoparticle drug delivery systems specifically targeted for melanoma were analyzed in this review article in relation to either their passive or their active cellular uptake mechanisms in order to deduce the efficacy of photodynamic therapy treatment for metastatic melanoma which currently remains ongoing. The overall findings from this review concluded that no current photodynamic therapy studies have been performed in relation to active nanoparticle platform photosensitizer drug carrier systems for the treatment of metastatic melanoma, and so this type of research requires further investigation into developing a more efficient active nano-photosensitizer carrier smart drug that can be conjugated to specific cell surface receptors and combinative monoclonal antibodies so that a further enhanced and more efficient form of targeted photodynamic therapy for the treatment of metastatic melanoma can be established.
| S-EPMC6090489 | biostudies-literature
Project description:Photodynamic therapy (PDT) using oxygen, light, and photosensitizers has been receiving great attention, because it has potential for making up for the weakness of the existing therapies such as surgery, radiation therapy, and chemotherapy. It has been mainly used to treat cancer, and clinical tests for second-generation photosensitizers with improved physicochemical properties, pharmacokinetic profiles, or singlet oxygen quantum yield have been conducted. Progress is also being made in cancer theranostics by using fluorescent signals generated by photosensitizers. In order to obtain the effective cytotoxic effects on the target cells and prevent off-target side effects, photosensitizers need to be localized to the target tissue. The use of nanocarriers combined with photosensitizers can enhance accumulation of photosensitizers in the tumor site, owing to preferential extravasation of nanoparticles into the tumor vasculature by the enhanced permeability and retention effect. Self-assembly of amphiphilic polymers provide good loading efficiency and sustained release of hydrophobic photosensitizers. In addition, prodrug nanomedicines for PDT can be activated by stimuli in the tumor site. In this review, we introduce current limitations and recent progress in nanomedicine for PDT and discuss the expected future direction of research.
| S-EPMC7830249 | biostudies-literature
Project description:Photodynamic diagnosis (PDD) and therapy (PDT) are emerging, non/minimally invasive techniques for cancer diagnosis and treatment. Both techniques require a photosensitizer and light to visualize or destroy cancer cells. However, a limitation of conventional, non-targeted PDT is poor selectivity, causing side effects. The bioconjugation of a photosensitizer to a tumor-targeting molecule, such as an antibody or a ligand peptide, is a way to improve selectivity. The bioconjugation strategy can generate a tumor-targeting photosensitizer conjugate specific for cancer cells, or ideally, for multiple tumor compartments to improve selectivity and efficacy, such as cancer stem cells and tumor neovasculature within the tumor microenvironment. If successful, such targeted photosensitizer conjugates can also be used for specific visualization and detection of cancer cells and/or tumor angiogenesis (an early event in tumorigenesis) with the hope of an early diagnosis of cancer. The purpose of this review is to summarize some current promising target molecules, e.g., tissue factor (also known as CD142), and the currently used bioconjugation strategies in PDT and PDD, with a focus on newly developed protein photosensitizers. These are genetically engineered photosensitizers, with the possibility of generating a fusion protein photosensitizer by recombinant DNA technology for both PDT and PDD without the need of chemical conjugation. We believe that providing an overview of promising targets and bioconjugation strategies will aid in driving research in this field forward towards more effective, less toxic, and non- or minimally invasive treatment and diagnosis options for cancer patients.
| S-EPMC7662882 | biostudies-literature
Project description:Photodynamic therapy (PDT) is a promising treatment modality for cancer management. So far, most PDT studies have focused on delivery of photosensitizers to tumors. O2, another essential component of PDT, is not artificially delivered but taken from the biological milieu. However, cancer cells demand a large amount of O2 to sustain their growth and that often leads to low O2 levels in tumors. The PDT process may further potentiate the oxygen deficiency, and in turn, adversely affect the PDT efficiency. In the present study, a new technology called red blood cell (RBC)-facilitated PDT, or RBC-PDT, is introduced that can potentially solve the issue. As the name tells, RBC-PDT harnesses erythrocytes, an O2 transporter, as a carrier for photosensitizers. Because photosensitizers are adjacent to a carry-on O2 source, RBC-PDT can efficiently produce 1O2 even under low oxygen conditions. The treatment also benefits from the long circulation of RBCs, which ensures a high intraluminal concentration of photosensitizers during PDT and hence maximizes damage to tumor blood vessels. When tested in U87MG subcutaneous tumor models, RBC-PDT shows impressive tumor suppression (76.7%) that is attributable to the codelivery of O2 and photosensitizers. Overall, RBC-PDT is expected to find wide applications in modern oncology.
| S-EPMC6867707 | biostudies-literature