Direct tumor damage mechanisms of photodynamic therapy.

Photodynamic therapy (PDT) is a clinically approved and rapidly developing cancer treatment regimen. It is a minimally invasive two-stage procedure that requires administration of a photosensitizing agent followed by illumination of the tumor with visible light usually generated by laser sources. A third component of PDT is molecular oxygen which is required for the most effective antitumor effects. In the presence of the latter, light of an appropriate wavelength excites the photosensitizer thereby producing cytotoxic intermediates that damage cellular structures. PDT has been approved in many countries for the treatment of lung, esophageal, bladder, skin and head and neck cancers. The antitumor effects of this treatment result from the combination of direct tumor cell photodamage, destruction of tumor vasculature and activation of an immune response. The mechanisms of the direct photodamage of tumor cells, the signaling pathways that lead to apoptosis or survival of sublethaly damaged cells, and potential novel strategies of improving the antitumor efficacy of PDT are discussed.

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Perspectives on the Role of Photodynamic Therapy in the Treatment of Pancreatic Cancer

International Journal of Photoenergy ◽

10.1155/2012/637429 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Wei Li ◽

Qingyong Ma ◽

Erxi Wu

Keyword(s):

Pancreatic Cancer ◽

Photodynamic Therapy ◽

Experimental Studies ◽

Oxygen Species ◽

Tumor Cell Death ◽

Antitumor Effects ◽

Immune System Activation ◽

System Activation ◽

Photosensitizing Agent

Photodynamic therapy (PDT) is a noninvasive procedure involving a photosensitizing agent that is activated by light to produce reactive oxygen species (ROS) that selectively destroy tumor cells. In recent years, PDT has been used in the treatment of pancreatic cancer (PC). The antitumor effects of PDT include three main mechanisms: direct tumor cell death (necrosis, apoptosis, and autophagy), vascular destruction, and immune system activation. The present paper systematically summarizes the effects of PDT in the treatment of PC from the experimental studies to the clinical studies and discusses the mechanisms of PDT-induced PC destruction.

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Photodynamic therapy: Promotion of efficacy by a sequential protocol

Journal of Porphyrins and Phthalocyanines ◽

10.1142/s1088424616500073 ◽

2016 ◽

Vol 20 (01n04) ◽

pp. 302-306 ◽

Cited By ~ 17

Author(s):

David Kessel

Keyword(s):

Photodynamic Therapy ◽

Tumor Vasculature ◽

Therapeutic Effects ◽

Current Development ◽

Apoptotic Response ◽

New Approach ◽

Tumor Cell Destruction ◽

Photosensitizing Agent ◽

Tumor Eradication ◽

Stimulation Of

Photodynamic therapy (PDT) offers a new approach to selective tumor eradication. Modifications designed to increase and optimize efficacy continue to emerge. Selective photodamage to malignant cells and their environment can bring about tumor cell destruction, shutdown of the tumor vasculature, stimulation of immunologic anti-tumor effects and potentiation of other therapeutic effects. Current development of combination protocols may provide a better rationale for integration of PDT into clinical practice. An example described here is the ability of a sequential (two-sensitizer) PDT protocol to enhance the efficacy of photokilling. The first step involves low-level lysosomal photodamage that has been shown to promote the apoptotic response to subsequent photodynamic effects directed at mitochondria. In this report, we demonstrate the ability of Photofrin, an FDA-approved photosensitizing agent, to serve as either the first or second element of the sequential protocol.

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Photodynamic Therapy for Laryngeal Cancers

Otorhinolaryngology Clinics - An International Journal ◽

10.5005/jp-journals-10003-1036 ◽

2010 ◽

Vol 2 (3) ◽

pp. 195-199

Author(s):

Merill Biel ◽

Kiskumar Thankappan ◽

Barbara Henderson ◽

Nestor Rigual

Keyword(s):

Photodynamic Therapy ◽

Minimally Invasive ◽

Laryngeal Cancer ◽

Alternative Treatment ◽

Patient Population ◽

Viable Alternative ◽

Invasive Treatment ◽

Novel Therapy ◽

Photosensitizing Agent

Abstract Laryngeal cancer can associated with significant long-term morbidities. Photodynamic (PDT), a minimally invasive treatment that uses light of a specific wavelength to activate a photosensitizing agent in the tumor and its microenvironment, offers a viable alternative treatment for this patient population without permanent treatment related sequelae. Our focus in this review is to discuss the existing evidence for the utilization PDT in treating laryngeal cancers and to summarize the advantages and limitations of this novel therapy.

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Immune Response Against Angiosarcoma Following Lower Fluence Rate Clinical Photodynamic Therapy

Journal of Environmental Pathology Toxicology and Oncology ◽

10.1615/jenvironpatholtoxicoloncol.v27.i1.40 ◽

2008 ◽

Vol 27 (1) ◽

pp. 35-42 ◽

Cited By ~ 25

Author(s):

Patricia S.P. Thong ◽

Malini Olivo ◽

Kiang-Wei Kho ◽

Ramaswamy Bhuvaneswari ◽

William W. L. Chin ◽

...

Keyword(s):

Immune Response ◽

Photodynamic Therapy ◽

Fluence Rate

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Optical Properties of Photodynamic Therapy Drugs in Different Environments: The Paradigmatic Case of Temoporfin

10.26434/chemrxiv.12118917.v2 ◽

2020 ◽

Author(s):

busenur Aslanoglu ◽

Ilya Yakavets ◽

Vladimir Zorin ◽

Henri-Pierre Lassalle ◽

Francesca Ingrosso ◽

...

Keyword(s):

Drug Delivery ◽

Optical Properties ◽

Photodynamic Therapy ◽

Minimally Invasive ◽

Visible Light ◽

Cancer Treatment ◽

Singlet Oxygen ◽

Tumor Cells ◽

Molecular Oxygen ◽

Computational Tools

Computational tools have been used to study the photophysical and photochemical features of photosensitizers in photodynamic therapy (PDT) –a minimally invasive, less aggressive alternative for cancer treatment. PDT is mainly based by the activation of molecular oxygen through the action of a photoexcited sensitizer (photosensitizer). Temoporfin, widely known as mTHPC, is a second-generation photosensitizer, which produces the cytotoxic singlet oxygen when irradiated with visible light and hence destroys tumor cells. However, the bioavailability of the mostly hydrophobic photosensitizer, and hence its incorporation into the cells, is fundamental to achieve the desired effect on malignant tissues by PDT. In this study, we focus on the optical properties of the temoporfin chromophore in different environments –in <i>vacuo</i>, in solution, encapsulated in drug delivery agents, namely cyclodextrin, and interacting with a lipid bilayer.

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Artificial Cell-Mediated Photodynamic Therapy Enhanced Anticancer Efficacy through Combination of Tumor Disruption and Immune Response Stimulation

ACS Omega ◽

10.1021/acsomega.9b01881 ◽

2019 ◽

Vol 4 (7) ◽

pp. 12727-12735 ◽

Cited By ~ 3

Author(s):

Jiang Ni ◽

Ying Sun ◽

Jinfang Song ◽

Yiqing Zhao ◽

Qiufang Gao ◽

...

Keyword(s):

Immune Response ◽

Photodynamic Therapy ◽

Anticancer Efficacy ◽

Artificial Cell

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RGD4C peptide mediates anti-p21Ras scFv entry into tumor cells and produces an inhibitory effect on the human colon cancer cell line SW480

BMC Cancer ◽

10.1186/s12885-021-08056-4 ◽

2021 ◽

Vol 21 (1) ◽

Cited By ~ 1

Author(s):

Chen-Chen Huang ◽

Fang-Rui Liu ◽

Qiang Feng ◽

Xin-Yan Pan ◽

Shu-Ling Song ◽

...

Keyword(s):

Antitumor Activity ◽

Cell Membrane ◽

Fusion Protein ◽

Tumor Cell ◽

Tumor Cells ◽

Fusion Proteins ◽

Inhibitory Effect ◽

Endosomal Escape ◽

Antitumor Effects ◽

Sw480 Cells

Abstract Background We prepared an anti-p21Ras scFv which could specifically bind with mutant and wild-type p21Ras. However, it cannot penetrate the cell membrane, which prevents it from binding to p21Ras in the cytoplasm. Here, the RGD4C peptide was used to mediate the scFv penetration into tumor cells and produce antitumor effects. Methods RGD4C-EGFP and RGD4C-p21Ras-scFv recombinant expression plasmids were constructed to express fusion proteins in E. coli, then the fusion proteins were purified with HisPur Ni-NTA. RGD4C-EGFP was used as reporter to test the factors affecting RGD4C penetration into tumor cell. The immunoreactivity of RGD4C-p21Ras-scFv toward p21Ras was identified by ELISA and western blotting. The ability of RGD4C-p21Ras-scFv to penetrate SW480 cells and colocalization with Ras protein was detected by immunocytochemistry and immunofluorescence. The antitumor activity of the RGD4C-p21Ras-scFv was assessed with the MTT, TUNEL, colony formation and cell migration assays. Chloroquine (CQ) was used an endosomal escape enhancing agent to enhance endosomal escape of RGD4C-scFv. Results RGD4C-p21Ras-scFv fusion protein were successfully expressed and purified. We found that the RGD4C fusion protein could penetrate into tumor cells, but the tumor cell entry of was time and concentration dependent. Endocytosis inhibitors and a low temperature inhibited RGD4C fusion protein endocytosis into cells. The change of the cell membrane potential did not affect penetrability. RGD4C-p21Ras-scFv could penetrate SW480 cells, effectively inhibit the growth, proliferation and migration of SW480 cells and promote this cells apoptosis. In addition, chloroquine (CQ) could increase endosomal escape and improve antitumor activity of RGD4C-scFv in SW480 cells. Conclusion The RGD4C peptide can mediate anti-p21Ras scFv entry into SW480 cells and produce an inhibitory effect, which indicates that RGD4C-p21Ras-scFv may be a potential therapeutic antibody for the treatment of ras-driven cancers.

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Metronomic photodynamic therapy using an implantable LED device and orally administered 5-aminolevulinic acid

Scientific Reports ◽

10.1038/s41598-020-79067-7 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Izumi Kirino ◽

Katsuhiko Fujita ◽

Kei Sakanoue ◽

Rin Sugita ◽

Kento Yamagishi ◽

...

Keyword(s):

Photodynamic Therapy ◽

Aminolevulinic Acid ◽

Antitumor Effects ◽

Continuous Irradiation ◽

Cancer Cell Death ◽

Long Duration ◽

Green Led ◽

Repeated Administrations ◽

532 Nm ◽

Patient Burden

AbstractMetronomic photodynamic therapy (mPDT) is a form of PDT that induces cancer cell death by intermittent continuous irradiation with a relatively weak power of light for a long duration (several days). We previously developed a wirelessly powered, fully implantable LED device and reported a significant anti-tumor effect of mPDT. Considering application in clinical practice, the method used for repeated administrations of photosensitizers required for mPDT should not have a high patient burden such as the burden of transvenous administration. Therefore, in this study, we selected 5-aminolevulinic acid (ALA), which can be administered orally, as a photosensitizer, and we studied the antitumor effects of mPDT. In mice with intradermal tumors that were orally administered ALA (200 mg/kg daily for 5 days), the tumor in each mouse was simultaneously irradiated (8 h/day for 5 days) using a wirelessly powered implantable green LED device (532 nm, 0.05 mW). Tumor growth in the mPDT-treated mice was suppressed by about half compared to that in untreated mice. The results showed that mPDT using the wirelessly powered implantable LED device exerted an antitumor effect even with the use of orally administered ALA, and this treatment scheme can reduce the burden of photosensitizer administration for a patient.

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