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Simple Summary: Photodynamic therapy (PDT) has emerged as a versatile treatment option for head and neck disorders. The purpose of our review was to provide an overview of the use of PDT therapy in a variety of diseases. The use of PDT therapy has recently emerged as an innovative and effective method of cancer treatment. However, more and more studies are showing that it is also promising for treating a variety of non-cancerous lesions, providing a minimally invasive alternative for certain conditions. The same following principles apply: the application of a photosensitizer, exposure to light, and then the destruction of abnormal cells. In our work, we highlighted the importance of photodynamic therapy and its valuable treatment as an option for a variety of diseases of the head and neck area, not just cancer. With this, we want to encourage researchers to more widely use photodynamic therapy in head and neck disorders. Photodynamic therapy (PDT) has emerged as a promising modality for the treatment of various diseases. This non-invasive approach utilizes photosensitizing agents and light to selectively target and destroy abnormal cells, providing a valuable alternative to traditional treatments. Research studies have explored the application of PDT in different areas of the head. Research is focusing on a growing number of new developments and treatments for cancer. One of these methods is PDT. Photodynamic therapy is now a revolutionary, progressive method of cancer therapy. A very important feature of PDT is that cells cannot become immune to singlet oxygen. With this therapy, patients can avoid lengthy and costly surgeries. PDT therapy is referred to as a safe and highly selective therapy. These studies collectively highlight the potential of PDT as a valuable therapeutic option in treating the head area. As research in this field progresses, PDT may become increasingly integrated into the clinical management of these conditions, offering a balance between effectiveness and minimal invasiveness. [ABSTRACT FROM AUTHOR]

Simple Summary: Near-infrared photoimmunotherapy (NIR-PIT) is a newly developed cancer treatment that uses photoreactive agents and light irradiation, while photodynamic therapy (PDT) is an existing phototherapy using photosensitizers and light irradiation as well as NIR-PIT. The current study investigated the properties of these therapies and their differences with a focus on their cellular binding/uptake specificity and cytotoxicity in vitro. NIR-PIT showed molecule-selective responses and cytotoxicity, whereas PDT showed non-selective cell type responses and cytotoxicity. Additionally, NIR-PIT and PDT induced damage-associated molecular patterns (DAMPs), a surrogate marker of immunogenic cell death, although PDT had different sensitivity between cell lines. Therefore, molecule-specific NIR-PIT may have advantages compared with PDT in terms of efficiency in tumor visualization and induction of DAMPs. Near-infrared photoimmunotherapy (NIR-PIT) is a new phototherapy that utilizes a monoclonal antibody (mAb) against cancer antigens and a phthalocyanine dye, IRDye700DX (IR700) conjugate (mAb-IR700). Photodynamic therapy (PDT) is a combination therapy that utilizes photoreactive agents and light irradiation as well as NIR-PIT. In the present study, we compared these therapies in vitro. The characterization of cellular binding/uptake specificity and cytotoxicity were examined using two mAb-IR700 forms and a conventional PDT agent, talaporfin sodium, in three cell lines. As designed, mAb-IR700 had high molecular selectivity and visualized target molecule-positive cells at the lowest concentration examined. NIR-PIT induced necrosis and damage-associated molecular patterns (DAMPs), a surrogate maker of immunogenic cell death. In contrast, talaporfin sodium was taken up by cells regardless of cell type, and its uptake was enhanced in a concentration-dependent manner. PDT induced cell death, with the pattern of cell death shifting from apoptosis to necrosis depending on the concentration of the photosensitizer. Induction of DAMPs was observed at the highest concentration, but their sensitivity differed among cell lines. Overall, our data suggest that molecule-specific NIR-PIT may have potential advantages compared with PDT in terms of the efficiency of tumor visualization and induction of DAMPs. [ABSTRACT FROM AUTHOR]

Simple Summary: Novel therapeutic modalities using medical devices have the potential to deliver effective treatment against the most aggressive form of primary brain tumour, Glioblastoma, for which there is currently no cure. These devices not only offer methods to enhance the effect of currently available therapies but also aim to provide innovative ways to deliver better therapeutic outcomes for this deadly disease. This review highlights recent innovations in this promising, growing field, and is intended to serve as a primer for clinicians, engineers and scientists interested in translating such technologies for the improvement of patient outcomes. Despite decades of research and the growing emergence of new treatment modalities, Glioblastoma (GBM) frustratingly remains an incurable brain cancer with largely stagnant 5-year survival outcomes of around 5%. Historically, a significant challenge has been the effective delivery of anti-cancer treatment. This review aims to summarize key innovations in the field of medical devices, developed either to improve the delivery of existing treatments, for example that of chemo-radiotherapy, or provide novel treatments using devices, such as sonodynamic therapy, thermotherapy and electric field therapy. It will highlight current as well as emerging device technologies, non-invasive versus invasive approaches, and by doing so provide a detailed summary of evidence from clinical studies and trials undertaken to date. Potential limitations and current challenges are discussed whilst also highlighting the exciting potential of this developing field. It is hoped that this review will serve as a useful primer for clinicians, scientists, and engineers in the field, united by a shared goal to translate medical device innovations to help improve treatment outcomes for patients with this devastating disease. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG) has been reported as a potential near-infrared (NIR) photosensitizer for photodynamic therapy (PDT) of cancer. However the application of ICG-mediated PDT is both intrinsically and physiologically limited. Here we report a combination of ICG-PDT with a chemotherapy drug etoposide (VP-16), aiming to enhance the anticancer efficacy, to circumvent limitations of PDT using ICG, and to reduce side effects of VP-16. We found in controlled in vitro cell-based assays that this combination is effective in killing non-small-cell lung cancer cells (NSCLC, A549 cell line). We also found that the combination of ICG-PDT and VP-16 exhibits strong synergy in killing non-small-cell lung cancer cells partially through inducing more DNA double-strand breaks (DSBs), while it has a much weaker synergy in killing human normal cells (GM05757). Furthermore, by studying the treatment sequence dependence and the cytotoxicity of laser-irradiated mixtures of ICG and VP-16, we found that the observed synergy involves direct/indirect reactions between ICG and VP-16. We further propose that there exists an electron transfer reaction between ICG and VP-16 under irradiation. This study therefore shows the anticancer efficacy of ICG-PDT combined with VP-16. These findings suggest that ICG-mediated PDT may be applied in combination with the chemotherapy drug VP-16 to treat some cancers, especially the non-small-cell lung cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. Numerous clinical trials evaluating various combinations of chemotherapy and targeted agents and radiotherapy have failed to provide meaningful improvements in survival. A growing number of studies however have indicated that photodynamic therapy (PDT) may be a viable approach for treatment of some pancreatic tumors. PDT, which uses light to activate a photosensitizing agent in target tissue, has seen widespread adoption primarily for dermatological and other applications where superficial light delivery is relatively straightforward. Advances in fiber optic light delivery and dosimetry however have been leveraged to enable PDT even for challenging internal sites, including the pancreas. The aim of this article is to help inform future directions by reviewing relevant literature on the basic science, current clinical status, and potential challenges in the development of PDT as a treatment for PDAC. Pancreatic ductal adenocarcinoma (PDAC) is among the most lethal of human cancers. Clinical trials of various chemotherapy, radiotherapy, targeted agents and combination strategies have generally failed to provide meaningful improvement in survival for patients with unresectable disease. Photodynamic therapy (PDT) is a photochemistry-based approach that enables selective cell killing using tumor-localizing agents activated by visible or near-infrared light. In recent years, clinical studies have demonstrated the technical feasibility of PDT for patients with locally advanced PDAC while a growing body of preclinical literature has shown that PDT can overcome drug resistance and target problematic and aggressive disease. Emerging evidence also suggests the ability of PDT to target PDAC stroma, which is known to act as both a barrier to drug delivery and a tumor-promoting signaling partner. Here, we review the literature which indicates an emergent role of PDT in clinical management of PDAC, including the potential for combination with other targeted agents and RNA medicine. [ABSTRACT FROM AUTHOR]

Simple Summary: The association between photodynamic therapy (PDT) and mortality in lung cancer patients remains unclear. We studied the association between PDT and mortality in patients with stage III/IV non-small cell lung cancer (NSCLC) using the National Cancer Database (NCDB) between 2004 and 2016. From the NCDB, we identified patients whose treatment code was ablation (including PDT). From Medicare and Medicaid data between 2000 and 2013, we identified NSCLC patients receiving PDT and used these to confirm PDT treatment. We assessed the association between PDT and mortality. Study groups consisted of 147 patients with PDT + radiation + chemotherapy, 227,629 with radiation + chemotherapy, 106,667 with radiation therapy alone and 122,193 with chemotherapy alone. Compared to the radiation alone group, the PDT group and radiation with chemotherapy group had lower risk of mortality (50% and 53% lower, respectively). Among the NSCLC patients with stage III or stage IV disease not eligible for surgery, the addition of PDT to chemotherapy and radiation therapy offers survival benefit over radiation therapy alone. Data regarding the association between photodynamic therapy (PDT) and mortality in lung cancer patients are limited. We analyzed the association between PDT and mortality in patients with stage III or IV non-small cell lung cancer (NSCLC) using data from the National Cancer Database (NCDB) between 2004 and 2016. From the NCDB, we identified patients receiving laser ablation/cryosurgery or local tumor destruction/excision (which includes PDT). From Medicare and Medicaid claims between 2000 and 2013, we identified NSCLC patients receiving PDT and those receiving bronchoscopy, then used these to confirm the PDT treatment. From NCDB, we extracted NSCLC patients who received radiation with chemotherapy, radiation alone or chemotherapy alone. We used survival analysis to determine the association between PDT and mortality. Between 2004 and 2016, 457,556 NSCLC patients with stage III or stage IV were identified, of which 147 received PDT with radiation and chemotherapy, 227,629 received radiation with chemotherapy, 106,667 had radiation therapy alone and 122,193 received chemotherapy alone. Compared to the radiation alone group, the PDT group and radiation with chemotherapy group had lower hazard of mortality (50% and 53% lower, respectively). Among the NSCLC patients with stage III or stage IV disease, the addition of PDT to radiation therapy offers survival benefit over radiation therapy alone. [ABSTRACT FROM AUTHOR]

Many studies have shown that low flux nitric oxide (NO) produced by inducible NO synthase (iNOS/NOS2) in various tumors, including glioblastomas, can promote angiogenesis, cell proliferation, and migration/invasion. Minimally invasive, site-specific photodynamic therapy (PDT) is a highly promising anti-glioblastoma modality. Recent research in the authors' laboratory has revealed that iNOS-derived NO in glioblastoma cells elicits resistance to 5-aminolevulinic acid (ALA)-based PDT, and moreover endows PDT-surviving cells with greater proliferation and migration/invasion aggressiveness. In this contribution, we discuss iNOS/NO antagonism to glioblastoma PDT and how this can be overcome by judicious use of pharmacologic inhibitors of iNOS activity or transcription. [ABSTRACT FROM AUTHOR]

Indocyanine green (ICG) has been reported as a potential near-infrared (NIR) photosensitizer for photodynamic therapy (PDT) of cancer. However the application of ICG-mediated PDT is both intrinsically and physiologically limited. Here we report a combination of ICG-PDT with a chemotherapy drug etoposide (VP-16), aiming to enhance the anticancer efficacy, to circumvent limitations of PDT using ICG, and to reduce side effects of VP-16. We found in controlled in vitro cell-based assays that this combination is effective in killing non-small-cell lung cancer cells (NSCLC, A549 cell line). We also found that the combination of ICG-PDT and VP-16 exhibits strong synergy in killing non-small-cell lung cancer cells partially through inducing more DNA double-strand breaks (DSBs), while it has a much weaker synergy in killing human normal cells (GM05757). Furthermore, by studying the treatment sequence dependence and the cytotoxicity of laser-irradiated mixtures of ICG and VP-16, we found that the observed synergy involves direct/indirect reactions between ICG and VP-16. We further propose that there exists an electron transfer reaction between ICG and VP-16 under irradiation. This study therefore shows the anticancer efficacy of ICG-PDT combined with VP-16. These findings suggest that ICG-mediated PDT may be applied in combination with the chemotherapy drug VP-16 to treat some cancers, especially the non-small-cell lung cancer., Competing Interests: The authors declare no conflict of interest.