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The morphology of cells undergoing apoptosis, necrosis, autophagy. Apoptotic cell showing characteristic cell shrinkage and apoptotic bodies densely packed with cell organelles. Necrotic cell showing dilated mitochondria and cell organelles due to increase in permeability of cell membrane to small charged molecules. Autophagic cell showing double membrane bound autophagosomal vacuoles sequestering the cytoplasmic contents including mitochondria, ribosomes.
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Though we crossed many milestones in the field of medicine and health care in eradicating some deadly diseases over the past decades, cancer remained a challenge taking the lives of millions of people and having adverse effects on the quality of life of survivors. Chemotherapy and radiotherapy, the two existing major treatment modalities, have seve...
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... The process then leads to irreversible cell damage and localized cell death [52,53]. Numerous advantages, including minimal toxicity to normal tissues, negligible systemic effects, protection of organ function, and high efficacy, make PDT a medical technique for the treatment of cancer patients [54]. The photosensitizer holds the major role in anti-tumor activity [44]. ...
Oral squamous-cell and pancreatic carcinomas are aggressive cancers with a poor outcome. Photodynamic therapy (PDT) consists of the use of photosensitizer-induced cell and tissue damage that is activated by exposure to visible light. PDT selectively acts on cancer cells, which have an accumulation of photosensitizer superior to that of the normal surrounding tissues. 5-aminolevulinic acid (5-ALA) induces the production of protoporphyrin IX (PpIX), an endogenous photosensitizer activated in PDT. This study aimed to test the effect of a new gel containing 5% v/v 5-ALA (ALAD-PDT) on human oral CAL-27 and pancreatic CAPAN-2 cancer cell lines. The cell lines were incubated in low concentrations of ALAD-PDT (0.05%, 0.10%, 0.20%, 0.40%, 0.75%, 1.0%) for 4 h or 8 h, and then irradiated for 7 min with 630 nm RED light. The cytotoxic effects of ALAD-PDT were measured using the MTS assay. Apoptosis, cell cycle, and ROS assays were performed using flow cytometry. PpIX accumulation was measured using a spectrofluorometer after 10 min and 24 and 48 h of treatment. The viability was extremely reduced at all concentrations, at 4 h for CAPAN-2 and at 8 h for CAL-27. ALAD-PDT induced marked apoptosis rates in both oral and pancreatic cancer cells. Elevated ROS production and appreciable levels of PpIX were detected in both cell lines. The use of ALA-PDT as a topical or intralesional therapy would permit the use of very low doses to achieve effective results and minimize side effects. ALAD-PDT has the potential to play a significant role in complex oral and pancreatic anticancer therapies.
... Under light irradiation, the PSs at ground singlet state can be first promoted to an excited singlet state and then go through intersystem crossing (ISC) to reach a triplet state. For Type-I PDT, triplet PSs can generate free radicals via hydrogen abstraction or electron transfer with surrounding substrates [6], while for Type-II PDT, triplet state PS transfers energy to molecular oxygen directly to form cytotoxic singlet oxygen ( 1 O 2 ) [7,8]. Indeed, in Type I, generated cytotoxic reactive oxygen synergistic chemo-phototherapy of breast cancer and the boosting of immunogenic cell death effects and systematic anti-tumor immunity responses. ...
Methylene blue (MB) is a well-established and extensively studied photosensitizer for photodynamic therapy (PDT), since it can generate singlet oxygen with a high quantum yield upon irradiation within the phototherapeutic (600–950 nm) window. However, its activity can decrease due to the formation of dimers or higher aggregates, which can take place in an aqueous solution at relatively high concentrations. The incorporation of this molecule into a matrix can avoid this aggregation and increase its activity relative to PDT. Silica porous nanoparticles are chosen here as a matrix to host MB. The size and pore geometry are tuned in order to decrease MB leaching while maintaining good singlet oxygen generation and colloidal stability for further applications in nanomedicine. In addition, phenyl functions are grafted on the pores of the silica matrix in order to avoid MB aggregation, thereby increasing the activity of the photosensitizer in the singlet oxygen generation. DFT calculations give insight in the structure of the aggregation of the MB units, and the roles of water and organic environments are investigated through time-dependent calculations on UV-vis spectra.
... One of their promising application regards the photodynamic therapy (PDT), a therapeutic treatment based on the use of light for different applications, including cancer, antimicrobial and environmental fields. [3][4][5] PDT is based on three essential components: light with proper wavelength, molecular oxygen and a photosensitizer (PS), a non-toxic molecule able to generate, under light irradiation, reactive oxygen species (ROS) lethal to cells. The absorption of one photon by the PSs leads to the population of their exited singlet states (S m ); these states are unstable and decay trough different pathways. ...
The outcomes of DFT‐based calculations are here reported to assess the applicability of two synthesized polypyridyl Ru(II) complexes, bearing ethynyl nile red (NR) on a bpy ligand, and two analogues, bearing modified‐NR, in photodynamic therapy. The absorption spectra, together with the non‐radiative rate constants for the S1 – Tn intersystem crossing transitions, have been computed for this purpose. Calculations evidence that the structural modification on the chromophore destabilizes the HOMO of the complexes thus reducing the H‐L gap and, consequently, red shifting the maximum absorption wavelength within the therapeutic window, up to 620 nm. Moreover, the favored ISC process from the bright state involves the triplet state closest in energy, which is also characterized by the highest SOC value and by the involvement of the whole bpy ligand bearing the chromophore in delocalising the unpaired electrons. These outcomes show that the photophysical behavior of the complexes is dominated by the chromophore.
... They also have an extended π-conjugation, which enables them to absorb visible light and have a high triplet yield. When illuminating, ROS are generated that have applications in the photodynamic therapy of cancer [104]. Recognizing the interactions of fullerenes with biomolecules is critical to unravel the mechanisms of their toxicity and to develop strategies to enhance their compatibility for use. ...
The physicochemical properties of group-XIV (G14) nanomaterials in the periodic table display a wide range of behaviors, making them a subject of significant interest in nanomedicine and nanobiotechnology due to their large surface area and low synthesis cost. Recently, there has been noteworthy development in the field of nanobiomedical research. Biomacromolecules can influence cell function primarily through cell-material surface interactions. Therefore, studying the interaction between G14-based nanomaterials and biomacromolecules like protein/DNA is a lucrative area of research that holds much promise. In this review, we offer a concise overview of the interaction between G14-based nanomaterials and protein/DNA. Furthermore, we explore their capacity to elicit structural variations from a bio-physicochemical perspective. We anticipate that this review will fundamentally contribute new perspectives to the application of G14-based nanomaterials in the fields of nanomedicine and pharmacy.
... First used for the treatment of skin cancers, then quickly extended to cancers of the prostate and the respiratory system, it is based on the combined action of three harmless components when taken separately: oxygen, photosensitive agents and light. Photodynamic therapy thus kills cancer cells by apoptosis, by producing reactive oxygen species (ROS) [2][3][4]. Photosensitive agents are introduced at the site of the tumor in the form of a cream for skin cancers or intravenously near the tumor for other cancers. These agents are absorbed within hours by cancer cells (preferably accumulate in rapidly growing cells) and then are activated by a light source of a specific wavelength, which causes them to react with the cell oxygen to form free radicals [5]. ...
This study demonstrates the potential of sono-photodynamic therapy as an effective approach for enhancing singlet oxygen generation using the synthesized Schiff-base diaxially substituted silicon phthalocyanines. In photochemical studies, the singlet oxygen quantum yields ( Φ ∆ ) were determined as 0.43 for Si1a , 0.94 for Q-Si1a , 0.58 for S-Si1a , and 0.49 for B-Sia1 . In sono-photochemical studies, the Φ ∆ values were reached to 0.67 for Si1a , 1.06 for Q-Si1a , 0.65 for S-Si1a , and 0.67 for B-Sia1 . In addition, this study demonstrates the therapeutic efficacy of phthalocyanines synthesized as sensitizers on the PC3 prostate cancer cell line through in vitro experiments. The application of these treatment modalities exhibited notable outcomes, leading to a substantial decrease in cell viability within the PC3 prostate cancer cell line. These findings highlight the potential of utilizing these synthesized phthalocyanines as promising therapeutic agents for prostate cancer treatment.
Graphical Abstract
... Combined regimens aim to increase the therapeutic efficiency of both therapies by additive or synergistic effects. The application of PDT plus chemotherapy is either to neutralize the pro-survival signals of PDT-resistant tumor cells or to weaken tumor cells to succumb to the PDT treatment that will occur later [27]. The relevance of this combination was perceived almost 30 years ago, with combinations between porphyrin and the chemotherapy drug chlorambucil [28] and since then efforts have been directed toward testing different therapies in combination with PDT, in vitro, in vivo and mainly, at the clinical level, with promising results for lung cancer [29][30][31][32], leukemia and lymphoma [33], cholangiocarcinoma [34], breast cancer [35][36][37], ovarian cancer [38,39] and melanoma [40]. ...
... The photochemical reactions that result in the formation of reactive oxygen species (ROS) responsible for cytotoxicity occur only when PS is irradiated with light and the area affected by the singlet oxygen is confined to a small volume due to its short lifetime (~3.5 ms in aqueous solution) and its inability to diffuse for distances greater than 100 nm into tissues. Thus, this treatment modality is considered noninvasive, relatively safe and selective, with minor systemic effects, significant reduction in long-term disease and lack of innate or acquired resistance mechanisms [25,27]. Although PDT may be an independent anticancer modality, the combination with other therapeutic methods can induce different cytotoxic pathways, initiating different cancer-fighting mechanisms, which result in greater therapeutic efficacy [71]. ...
Introduction:
Despite the evidence that photodynamic therapy (PDT) associated with chemotherapy presents great potential to overcome the limitations of monotherapy, little is known about the current status of this combination against cervical cancer. This systematic review aimed to address the currently available advances in combining PDT and chemotherapy in different research models and clinical trials of cervical cancer.
Methods:
We conducted a systematic review based on PRISMA Statement and Open Science Framework review protocol using PubMed, Web of Science, Embase, Scopus, LILACS, and Cochrane databases. We selected original articles focusing on 'Uterine Cervical Neoplasms' and 'Photochemotherapy and Chemotherapy' published in the last 10 years. The risk of bias in the studies was assessed using the CONSORT and SYRCLE tools.
Results:
Twenty-three original articles were included, focusing on HeLa cells, derived from endocervical adenocarcinoma and on combinations of several chemotherapeutics. Most of the combinations used modern drug delivery systems for improved simultaneous delivery and presented promising results with increased cytotoxicity compared to monotherapy.
Conclusion:
Despite the scarcity of animal studies and the absence of clinical studies, the combination of chemotherapy with PDT presents a potential option for cervical cancer therapy requiring additional studies.
Osf registration:
https://doi.org/10.17605/OSF.IO/WPHN5 [Figure: see text].
... [10] Other uses of photosensitizers are in photon upconversion [11] and photodynamic therapy. [12] ...
The regioselective synthesis of biphenyls, which are economically important pharmaceuticals, agrochemicals, and liquid crystals, is a challenging task. Current methods rely on metal‐dependent cross‐coupling reactions, which unfortunately require the use of harmful halogenated aryls and heavy metal catalysts that are toxic and difficult to remove from the final products. Recently, we have circumvented these problems by developing a metal‐free and broadly applicable photochemical method for biphenyl synthesis using UV−C light, called photosplicing. Here we present an improved method using photosensitizers in combination with UV−B, UV−A light, or sunlight. Using a high‐precision flow reactor with deep‐UV LEDs, we investigated the ability of commonly available organic photosensitizers to enhance the photosplicing reaction and identified a number of suitable photosensitizers with the required triplet energy. This method allows for easy batch synthesis of biaryls in borosilicate glassware and paves the way for their large‐scale production without the need for flow reactors.
... and viruses. Singlet oxygen ( 1 O 2 ) is known for its powerful oxidation properties (Chilakamarthi and Giribabu, 2017;Kwiatkowski et al., 2018). The ROS produced in PDT have the capacity to oxidize amino acid residues, consequently inhibiting the assembly of AB monomers to form AB aggregates. ...
Alzheimer's disease (AD), referring to a gradual deterioration in cognitive function, including memory loss and impaired thinking skills, has emerged as a substantial worldwide challenge with profound social and economic implications. As the prevalence of AD continues to rise and the population ages, there is an imperative demand for innovative imaging techniques to help improve our understanding of these complex conditions. Photoacoustic (PA) imaging forms a hybrid imaging modality by integrating the high-contrast of optical imaging and deep-penetration of ultrasound imaging. PA imaging enables the visualization and characterization of tissue structures and multifunctional information at high resolution and, has demonstrated promising preliminary results in the study and diagnosis of AD. This review endeavors to offer a thorough overview of the current applications and potential of PA imaging on AD diagnosis and treatment. Firstly, the structural, functional, molecular parameter changes associated with AD-related brain imaging captured by PA imaging will be summarized, shaping the diagnostic standpoint of this review. Then, the therapeutic methods aimed at AD is discussed further. Lastly, the potential solutions and clinical applications to expand the extent of PA imaging into deeper AD scenarios is proposed. While certain aspects might not be fully covered, this mini-review provides valuable insights into AD diagnosis and treatment through the utilization of innovative tissue photothermal effects. We hope that it will spark further exploration in this field, fostering improved and earlier theranostics for AD.
... Many studies have focused on activating death pathways that encourage an immune response in tumor cells, and positive findings suggest that ICD triggered by photoimmunotherapy is an area of significant investigation. Notably, certain tumors, such as mammary carcinoma 4T1, melanoma B16F10, and colon adenocarcinoma CT26, exhibit increased immunogenic potential for immunogenic PDT [73][74][75][76][77][78][79]. ICD-PDT is used for the treatment of highly challenging and life-threatening tumors, such as glioma, which are usually resistant to traditional therapies [30,80]. ...
The development of cancer immunotherapy approaches gives hope to millions of patients for a better clinical outcome after tumor treatment. Investigating the fundamental mechanisms of antitumor immunity activation is an urgent task. The induction of immunogenic cell death is told by many authors, although the process is elegant and simple. Different stimuli can be brought to ICD, but photodynamic exposure has proven to be an effective inducer of programmed death on par with radiotherapy. The link between triggering a photodynamic response on cancer cells and triggering immunogenic cell death has been poorly described in experimental work. The question of which molecular cascades are activated after PDT irradiation and how they lead to the release of DAMPs is intriguing. Much is known about ROS generation and endoplasmic reticulum stress, but rarely about the Golgi apparatus. Photosensitizers of different natures can lead to different effects, including completely nonimmunogenic ones. In this review, we describe the cascades that link the induction of cell death by photodynamic exposure and the immunogenic pattern of DAMPs release. We discuss those photosensitizers that have shown potential as ICD inducers and talk about the different pathways of programmed death that occur during PDT exposure.
... In 1948, 44 years later, Figge proved that porphyrins-now common photosensitizers (PSs)-tend to be stored in tumor cells in mice [1]. The topic of cancer treatment with PDT has been developed by subsequent researchers from generation to generation [2]. Currently, PDT appears to be a promising method for treating mainly cancerous conditions [3,4]. ...
The origins of photodynamic therapy (PDT) date back to 1904. Since then, the amount of research proving PDT and, consequently, its applicability to various disease states has steadily increased. Currently, PDT is mainly used in oncology to destroy cancer cells. It is being worked on for possible use in other medical fields as well, including cardiology. It can be used in the prevention of restenosis, often occurring after vascular surgical interventions, for destroying atherosclerotic plaques and as a new ablative method of ectopic centers in the treatment of atrial fibrillation. The purpose of this review is to summarize the knowledge to date regarding the therapeutic potential of using PDT for various pathological conditions in cardiology. The review also focuses on the current limitations associated with the use of PDT and identifies areas where more research is needed to develop better drug regimens. Materials and methods: The study analyzed 189 medical articles. The articles came from PubMed, Frontiers, Google Scholar, Science Direct and Web of Science databases. Through the excitation of light, a photosensitizer (PS) introduced into the body, the destruction of pathological cells occurs. PTD is widely used in oncology of the central nervous system (CNS). This process is made possible by the production of free oxygen radicals (ROS) and singlet oxygen, which generate oxidative stress that destroys sensitive cancer cells. In recent years, photosensitizers have also been discovered to have a strong affinity for macrophages that fill atherosclerotic plaques, making these compounds suitable for treating atherosclerosis. By inducing apoptosis of smooth muscle cells, inactivating basic fibroblast growth factor (FGF-β) and inhibiting endothelial cell hyperplasia, PDT can be used to prevent restenosis after surgical proceduresPDT appears to be a minimally invasive and highly effective therapeutic method, especially when combined with other therapeutic methods. Unfortunately, the small number of animal model studies and human clinical trials greatly limit the applicability of PDT on a wider scale. Current limitations, such as the depth of penetration, delivery of photosensitizer particles to the direct site of the lesion or the appropriate choice of photosensitizer in relation to the nature of the pathology, unfortunately make it impossible to replace current therapeutic approaches.
