scholarly journals The Cisplatin-Derived Increase of Mitochondrial Reactive Oxygen Species Enhances the Effectiveness of Photodynamic Therapy via Transporter Regulation

Cells ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 918 ◽  
Author(s):  
Hiromi Kurokawa ◽  
Hiromu Ito ◽  
Hirofumi Matsui
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Cancer Cell ◽  
Aminolevulinic Acid ◽  
Reactive Oxygen ◽  
Peptide Transporter ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Cancer Tissues

Photodynamic therapy (PDT) is a cancer treatment involving the generation of reactive oxygen species (ROS) by laser irradiation of porphyrins that accumulate in cancer tissues. 5-aminolevulinic acid (ALA), a porphyrin precursor, is often used as a photosensitizer. ALA is imported into cells via peptide transporter 1 (PEPT1), and porphyrin is exported via ATP-binding cassette member 2 of subfamily G (ABCG2). Thus, cancer cell-specific porphyrin accumulation involves regulation of both transporters to enhance the ALA-PDT effect. We reported previously that mitochondrial ROS (mitROS) upregulated PEPT1 expression and downregulated ABCG2 expression. Therefore, we propose that increasing mitROS production will enhance ALA-PDT cytotoxicity. Cisplatin is a chemotherapeutic drug that induces intracellular ROS generation. In this study, we investigated whether cisplatin-increased mitROS production in gastric cancer cell lines (RGK36 and RGK45) enhanced the cytotoxicity of ALA-PDT by regulation the expression of both PEPT1 and ABCG2. The results showed that cisplatin increased intracellular mitROS production in cancer but not normal cells (RGM1). PEPT1 was upregulated and ABCG2 downregulated in cancer cells treated with cisplatin. Moreover, intracellular porphyrin accumulation and ALA-PDT cytotoxicity increased. We conclude that cisplatin treatment increases the intracellular mitROS concentration and upregulates PEPT1 and downregulates ABCG2 expression.

scholarly journals Binary organic nanoparticles with enhanced reactive oxygen species generation capability for photodynamic therapy

2021 ◽  
pp. 2150009
Author(s):  
Xiaofu Weng ◽  
Zhouzhou Bao ◽  
Xunbin Wei
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Tumor Targeting ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Enhanced Fluorescence ◽  
New Strategy ◽  
Biological Environment

Photodynamic therapy (PDT) takes advantage of photosensitizers (PSs) to generate reactive oxygen species (ROS) for cell killing when excited by light. It has been widely used in clinic for therapy of multiple cancers. Currently, all the FDA-approved PSs, including porphyrin, are all small organic molecules, suffering from aggregation-caused quenching (ACQ) issues in biological environment and lacking tumor targeting capability. Nanoparticles (NPs) with size between 20[Formula: see text]nm and 200[Formula: see text]nm possess tumor targeting capability due to the enhanced permeability and retention (EPR) effect. It is urgent to develop a new strategy to form clinical-approved-PSs-based NPs with improved ROS generation capability. In this study, we report a strategy to overwhelm the ACQ of porphyrin by doping it with a type of aggregation-induced emission (AIE) luminogen to produce a binary NPs with high biocompatibility, and enhanced fluorescence and ROS generation capability. Such NPs can be readily synthesized by mixing a porphyrin derivative, Ce6 with a typical AIE luminogen, TPE-Br. Here, our experimental results have demonstrated the feasibility and effectiveness of this strategy, endowing it a great potential in clinical applications.

A photo and tumor microenvironment activated nano-enzyme with enhanced ROS generation and hypoxia relief for efficient cancer therapy

2021 ◽  
Vol 9 (39) ◽  
pp. 8253-8262
Author(s):  
Yali Chen ◽  
Yujun Cai ◽  
Xingsu Yu ◽  
Hong Xiao ◽  
Haozhe He ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Tumor Therapy ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Therapy Strategies

Reactive oxygen species (ROS) mediated tumor therapy strategies have exhibited great prospects and attracted increasing attention, among which photodynamic therapy (PDT) has been well-established.

Synthesis and evaluation of new 5-aminolevulinic acid derivatives as prodrugs of protoporphyrin for photodynamic therapy

2017 ◽  
Vol 16 (11) ◽  
pp. 1623-1630 ◽  
Author(s):  
Wei Zhu ◽  
Ying-Hua Gao ◽  
Chun-Hong Song ◽  
Zhi-Bin Lu ◽  
Tabbisa Namulinda ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Aminolevulinic Acid ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Light Activation ◽  
S180 Cell

Upon light activation, 13a can induce the production of PpIX in vivo which produces ROS and other reactive oxygen species to lead to the apoptosis of S180 cell tumors.

scholarly journals Cross talk between increased intracellular zinc (Zn2+) and accumulation of reactive oxygen species in chemical ischemia

2017 ◽  
Vol 313 (4) ◽  
pp. C448-C459 ◽  
Author(s):  
Kira G. Slepchenko ◽  
Qiping Lu ◽  
Yang V. Li
Keyword(s):  
Reactive Oxygen Species ◽  
Nadph Oxidase ◽  
Cross Talk ◽  
Reactive Oxygen ◽  
Glucose Deprivation ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Ros Accumulation ◽  
Ischemic Stress

Both zinc (Zn2+) and reactive oxygen species (ROS) have been shown to accumulate during hypoxic-ischemic stress and play important roles in pathological processes. To understand the cross talk between the two of them, here we studied Zn2+ and ROS accumulation by employing fluorescent probes in HeLa cells to further the understanding of the cause and effect relationship of these two important cellular signaling systems during chemical-ischemia, stimulated by oxygen and glucose deprivation (OGD). We observed two Zn2+ rises that were divided into four phases in the course of 30 min of OGD. The first Zn2+ rise was a transient, which was followed by a latent phase during which Zn2+ levels recovered; however, levels remained above a basal level in most cells. The final phase was the second Zn2+ rise, which reached a sustained plateau called Zn2+ overload. Zn2+ rises were not observed when Zn2+ was removed by TPEN (a Zn2+ chelator) or thapsigargin (depleting Zn2+ from intracellular stores) treatment, indicating that Zn2+ was from intracellular storage. Damaging mitochondria with FCCP significantly reduced the second Zn2+ rise, indicating that the mitochondrial Zn2+ accumulation contributes to Zn2+ overload. We also detected two OGD-induced ROS rises. Two Zn2+ rises preceded two ROS rises. Removal of Zn2+ reduced or delayed OGD- and FCCP-induced ROS generation, indicating that Zn2+ contributes to mitochondrial ROS generation. There was a Zn2+-induced increase in the functional component of NADPH oxidase, p47phox, thus suggesting that NADPH oxidase may mediate Zn2+-induced ROS accumulation. We suggest a new mechanism of cross talk between Zn2+ and mitochondrial ROS through positive feedback processes that eventually causes excessive free Zn2+ and ROS accumulations during the course of ischemic stress.

scholarly journals Combination of photodynamic therapy (PDT) and anti-tumor immunity in cancer therapy

2018 ◽  
Vol 48 (2) ◽  
pp. 143-151 ◽  
Author(s):  
Hee Sook Hwang ◽  
Heejun Shin ◽  
Jieun Han ◽  
Kun Na
Keyword(s):  
Reactive Oxygen Species ◽  
Immune Response ◽  
Cell Death ◽  
Photodynamic Therapy ◽  
Adaptive Immune Response ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Tumor Cell Death ◽  
Target Sites

Abstract Photodynamic therapy (PDT) is performed using a photosensitizer and light of specific wavelength in the presence of oxygen to generate singlet oxygen and reactive oxygen species(ROS) in the cancer cells. The accumulated photosensitizers in target sites induce ROS generation upon light activation, then the generated cytotoxic reactive oxygen species lead to tumor cell death via apoptosis or necrosis, and damages the target sites which results tumor destruction. As a consequence, the PDT-mediated cell death is associated with anti-tumor immune response. In this paper, the effects of PDT and immune response on tumors are reviewed. Activation of an immune response regarding the innate and adaptive immune response, interaction with immune cells and tumor cells that associated with antitumor efficacy of PDT are also discussed.

scholarly journals Reactive Oxygen Species (Ros-Induced) Ros Release

2000 ◽  
Vol 192 (7) ◽  
pp. 1001-1014 ◽  
Author(s):  
Dmitry B. Zorov ◽  
Charles R. Filburn ◽  
Lars-Oliver Klotz ◽  
Jay L. Zweier ◽  
Steven J. Sollott
Keyword(s):  
Reactive Oxygen Species ◽  
Cardiac Myocytes ◽  
Cell Biology ◽  
Mitochondrial Permeability Transition ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Ros Scavenging ◽  
Mitochondrial Ros ◽  
Ros Accumulation

We sought to understand the relationship between reactive oxygen species (ROS) and the mitochondrial permeability transition (MPT) in cardiac myocytes based on the observation of increased ROS production at sites of spontaneously deenergized mitochondria. We devised a new model enabling incremental ROS accumulation in individual mitochondria in isolated cardiac myocytes via photoactivation of tetramethylrhodamine derivatives, which also served to report the mitochondrial transmembrane potential, ΔΨ. This ROS accumulation reproducibly triggered abrupt (and sometimes reversible) mitochondrial depolarization. This phenomenon was ascribed to MPT induction because (a) bongkrekic acid prevented it and (b) mitochondria became permeable for calcein (∼620 daltons) concurrently with depolarization. These photodynamically produced “triggering” ROS caused the MPT induction, as the ROS scavenger Trolox prevented it. The time required for triggering ROS to induce the MPT was dependent on intrinsic cellular ROS-scavenging redox mechanisms, particularly glutathione. MPT induction caused by triggering ROS coincided with a burst of mitochondrial ROS generation, as measured by dichlorofluorescein fluorescence, which we have termed mitochondrial “ROS-induced ROS release” (RIRR). This MPT induction/RIRR phenomenon in cardiac myocytes often occurred synchronously and reversibly among long chains of adjacent mitochondria demonstrating apparent cooperativity. The observed link between MPT and RIRR could be a fundamental phenomenon in mitochondrial and cell biology.

scholarly journals Nanocomposites for X-Ray Photodynamic Therapy

2020 ◽  
Vol 21 (11) ◽  
pp. 4004 ◽  
Author(s):  
Zaira Gadzhimagomedova ◽  
Peter Zolotukhin ◽  
Oleg Kit ◽  
Daria Kirsanova ◽  
Alexander Soldatov
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Metal Organic Frameworks ◽  
Reactive Oxygen ◽  
Modern Medicine ◽  
Oxygen Species ◽  
X Rays ◽  
X Ray ◽  
Metal Organic ◽  
Cancer Tissues

Photodynamic therapy (PDT) has long been known as an effective method for treating surface cancer tissues. Although this technique is widely used in modern medicine, some novel approaches for deep lying tumors have to be developed. Recently, deeper penetration of X-rays into tissues has been implemented, which is now known as X-ray photodynamic therapy (XPDT). The two methods differ in the photon energy used, thus requiring the use of different types of scintillating nanoparticles. These nanoparticles are known to convert the incident energy into the activation energy of a photosensitizer, which leads to the generation of reactive oxygen species. Since not all photosensitizers are found to be suitable for the currently used scintillating nanoparticles, it is necessary to find the most effective biocompatible combination of these two agents. The most successful combinations of nanoparticles for XPDT are presented. Nanomaterials such as metal–organic frameworks having properties of photosensitizers and scintillation nanoparticles are reported to have been used as XPDT agents. The role of metal–organic frameworks for applying XPDT as well as the mechanism underlying the generation of reactive oxygen species are discussed.

scholarly journals Significance of Mitochondrial Reactive Oxygen Species in the Generation of Oxidative Stress in Spermatozoa

2008 ◽  
Vol 93 (8) ◽  
pp. 3199-3207 ◽  
Author(s):  
Adam J. Koppers ◽  
Geoffry N. De Iuliis ◽  
Jane M. Finnie ◽  
Eileen A. McLaughlin ◽  
R. John Aitken
Keyword(s):  
Oxidative Stress ◽  
Reactive Oxygen Species ◽  
Complex I ◽  
Mitochondrial Membrane ◽  
Reactive Oxygen ◽  
Human Spermatozoa ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Ros ◽  
Sperm Movement

Abstract Context: Male infertility has been linked with the excessive generation of reactive oxygen species (ROS) by defective spermatozoa. However, the subcellular origins of this activity are unclear. Objective: The objective of this study was to determine the importance of sperm mitochondria in creating the oxidative stress associated with defective sperm function. Method: Intracellular measurement of mitochondrial ROS generation and lipid peroxidation was performed using the fluorescent probes MitoSOX red and BODIPY C11 in conjunction with flow cytometry. Effects on sperm movement were measured by computer-assisted sperm analysis. Results: Disruption of mitochondrial electron transport flow in human spermatozoa resulted in generation of ROS from complex I (rotenone sensitive) or III (myxothiazol, antimycin A sensitive) via mechanisms that were independent of mitochondrial membrane potential. Activation of ROS generation at complex III led to the rapid release of hydrogen peroxide into the extracellular space, but no detectable peroxidative damage. Conversely, the induction of ROS on the matrix side of the inner mitochondrial membrane at complex I resulted in peroxidative damage to the midpiece and a loss of sperm movement that could be prevented by the concomitant presence of α-tocopherol. Defective human spermatozoa spontaneously generated mitochondrial ROS in a manner that was negatively correlated with motility. Simultaneous measurement of general cellular ROS generation with dihydroethidium indicated that 68% of the variability in such measurements could be explained by differences in mitochondrial ROS production. Conclusion: We conclude that the sperm mitochondria make a significant contribution to the oxidative stress experienced by defective human spermatozoa.

Multifunctional UCNPs@MnSiO3@g-C3N4 nanoplatform: improved ROS generation and reduced glutathione levels for highly efficient photodynamic therapy

2017 ◽  
Vol 5 (12) ◽  
pp. 2456-2467 ◽  
Author(s):  
Lili Feng ◽  
Fei He ◽  
Yunlu Dai ◽  
Shili Gai ◽  
Chongna Zhong ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Photodynamic Therapy ◽  
Cancer Treatment ◽  
Reduced Glutathione ◽  
Reactive Oxygen ◽  
Ros Generation ◽  
Oxygen Species ◽  
Malignant Cells ◽  
Novel Technique ◽  
Highly Efficient

Photodynamic therapy (PDT) is a novel technique that has been extensively employed in cancer treatment; it utilizes reactive oxygen species to kill malignant cells.

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