Tumor Microenvironment‐activated Reactive Oxygen Species Amplifier for Enzymatic Cascade Cancer Starvation/Chemodynamic /Immunotherapy

2021 ◽  
pp. 2106010
Author(s):  
Man Wang ◽  
Mengyu Chang ◽  
Chunxia Li ◽  
Qing Chen ◽  
Zhiyao Hou ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Microenvironment ◽  
Reactive Oxygen ◽  
Oxygen Species

scholarly journals Tumor-Specific Reactive Oxygen Species Accelerators Improve Chimeric Antigen Receptor T Cell Therapy in B Cell Malignancies

2019 ◽  
Vol 20 (10) ◽  
pp. 2469 ◽  
Author(s):  
Hyeon Joo Yoo ◽  
Yibin Liu ◽  
Lei Wang ◽  
Maria-Luisa Schubert ◽  
Jean-Marc Hoffmann ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Reactive Oxygen ◽  
Treatment Resistance ◽  
Lymphocytic Leukemia ◽  
Oxygen Species ◽  
T Cell Therapy

Chimeric antigen receptor T cell (CART) therapy is currently one of the most promising treatment approaches in cancer immunotherapy. However, the immunosuppressive nature of the tumor microenvironment, in particular increased reactive oxygen species (ROS) levels, provides considerable limitations. In this study, we aimed to exploit increased ROS levels in the tumor microenvironment with prodrugs of ROS accelerators, which are specifically activated in cancer cells. Upon activation, ROS accelerators induce further generation of ROS. This leads to an accumulation of ROS in tumor cells. We hypothesized that the latter cells will be more susceptible to CARTs. CD19-specific CARTs were generated with a CD19.CAR.CD28.CD137zeta third-generation retroviral vector. Cytotoxicity was determined by chromium-51 release assay. Influence of the ROS accelerators on viability and phenotype of CARTs was determined by flow cytometry. The combination of CARTs with the ROS accelerator PipFcB significantly increased their cytotoxicity in the Burkitt lymphoma cell lines Raji and Daudi, as well as primary chronic lymphocytic leukemia cells. Exposure of CARTs to PipFcB for 48 h did not influence T cell exhaustion, viability, or T cell subpopulations. In summary, the combination of CARTs with ROS accelerators may improve adoptive immunotherapy and help to overcome tumor microenvironment-mediated treatment resistance.

scholarly journals Ultrasound-induced reactive oxygen species generation and mitochondria-specific damage by sonodynamic agent/metal ion-doped mesoporous silica

RSC Advances ◽  
2019 ◽  
Vol 9 (68) ◽  
pp. 39924-39931 ◽  
Author(s):  
Kecan Lin ◽  
Ziguo Lin ◽  
Yujie Li ◽  
Youshi Zheng ◽  
Da Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Microenvironment ◽  
Cancer Therapy ◽  
Mesoporous Silica ◽  
Metal Ion ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species

Herein, we design tumor microenvironment specific active nano sono-chemodynamic agent for synergistic photodynamic–chemodynamic cancer therapy.

scholarly journals STIM-Orai Channels and Reactive Oxygen Species in the Tumor Microenvironment

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 457 ◽  
Author(s):  
Janina Frisch ◽  
Adrian Angenendt ◽  
Markus Hoth ◽  
Leticia Prates Roma ◽  
Annette Lis
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Blood Vessels ◽  
Cancer Cell ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Soluble Factors ◽  
Orai Channels

The tumor microenvironment (TME) is shaped by cancer and noncancerous cells, the extracellular matrix, soluble factors, and blood vessels. Interactions between the cells, matrix, soluble factors, and blood vessels generate this complex heterogeneous microenvironment. The TME may be metabolically beneficial or unbeneficial for tumor growth, it may favor or not favor a productive immune response against tumor cells, or it may even favor conditions suited to hijacking the immune system for benefitting tumor growth. Soluble factors relevant for TME include oxygen, reactive oxygen species (ROS), ATP, Ca2+, H+, growth factors, or cytokines. Ca2+ plays a prominent role in the TME because its concentration is directly linked to cancer cell proliferation, apoptosis, or migration but also to immune cell function. Stromal-interaction molecules (STIM)-activated Orai channels are major Ca2+ entry channels in cancer cells and immune cells, they are upregulated in many tumors, and they are strongly regulated by ROS. Thus, STIM and Orai are interesting candidates to regulate cancer cell fate in the TME. In this review, we summarize the current knowledge about the function of ROS and STIM/Orai in cancer cells; discuss their interdependencies; and propose new hypotheses how TME, ROS, and Orai channels influence each other.

Reactive Oxygen Species–Activatable Liposomes Regulating Hypoxic Tumor Microenvironment for Synergistic Photo/Chemodynamic Therapies

2019 ◽  
Vol 29 (44) ◽  
pp. 1905013 ◽  
Author(s):  
Zhihao Zhao ◽  
Weiqi Wang ◽  
Chenxi Li ◽  
Yiqiu Zhang ◽  
Tianrong Yu ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Microenvironment ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Hypoxic Tumor

Grade-targeted nanoparticles for improved hypoxic tumor microenvironment and enhanced photodynamic cancer therapy

Nanomedicine ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. 221-235 ◽  
Author(s):  
Ying-kai Tao ◽  
Xiao-yang Hou ◽  
Huan Gao ◽  
Xin Zhang ◽  
Feng-mei Zuo ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Microenvironment ◽  
Aminolevulinic Acid ◽  
Double Emulsion ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
In Vivo Experiments ◽  
Limited Diffusion

Background: The hypoxia of the tumor microenvironment (TME), low transfer efficiency of photosensitizers and limited diffusion distance of reactive oxygen species restrict the application of photodynamic therapy (PDT). Aim: To produce TME-responsive and effective nanoparticles for sensitizing PDT. Materials & methods: CD44 and mitochondria grade-targeted hyaluronic acid (HA)-triphenylphosphine (TPP)-aminolevulinic acid (ALA)-catalase (CAT) nanoparticles (HTACNPs) were synthesized via a modified double-emulsion method. In vitro and in vivo experiments were performed to investigate the antitumor efficacy of HTACNP-mediated PDT. Results: HTACNPs specifically targeted MV3 cells and the mitochondria and produced O2 to relieve TME hypoxia. HTACNP-mediated PDT produced reactive oxygen species to induce irreversible cell apoptosis. HTACNP-PDT inhibited melanoma growth effectively in vivo. Conclusion: HTACNP-mediated PDT improved TME hypoxia and effectively enhanced PDT for cancer.

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.

scholarly journals Reactive Oxygen Species in the Tumor Microenvironment: An Overview

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1191 ◽  
Author(s):  
Frank Weinberg ◽  
Nithya Ramnath ◽  
Deepak Nagrath
Keyword(s):  
Reactive Oxygen Species ◽  
Tumor Microenvironment ◽  
Reactive Oxygen ◽  
Physiological Effects ◽  
Oxygen Species ◽  
Proliferative Effect ◽  
Low Levels ◽  
Cellular Components ◽  
Anti Tumor Activity ◽  
Insight Into

Reactive oxygen species (ROS) are important signaling molecules in cancer. The level of ROS will determine physiological effects. While high levels of ROS can cause damage to tissues and cell death, low levels of ROS can have a proliferative effect. ROS are produced by tumor cells but also cellular components that make up the tumor microenvironment (TME). In this review, we discuss the mechanisms by which ROS can affect the TME with particular emphasis on tumor-infiltrating leukocytes. Greater insight into ROS biology in this setting may allow for therapeutic manipulation of ROS levels in order to remodel the tumor microenvironment and increase anti-tumor activity.

scholarly journals Reactive Oxygen Species-Mediated Tumor Microenvironment Transformation: The Mechanism of Radioresistant Gastric Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Huifeng Gu ◽  
Tianhe Huang ◽  
Yicheng Shen ◽  
Yin Liu ◽  
Fuling Zhou ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Reactive Oxygen Species ◽  
Tumor Microenvironment ◽  
Epithelial Mesenchymal Transition ◽  
Reactive Oxygen ◽  
Inflammatory Cells ◽  
Inflammatory Factors ◽  
Oxygen Species ◽  
Mesenchymal Transition ◽  
Development Of Gastric Cancer

Radioresistance is one of the primary causes responsible for therapeutic failure and recurrence of cancer. It is well documented that reactive oxygen species (ROS) contribute to the initiation and development of gastric cancer (GC), and the levels of ROS are significantly increased in patients with GC accompanied with abnormal expressions of multiple inflammatory factors. It is also well documented that ROS can activate cancer cells and inflammatory cells, stimulating the release of a variety of inflammatory cytokines, which subsequently mediates the tumor microenvironment (TME) and promotes cancer stem cell (CSC) maintenance as well as renewal and epithelial-mesenchymal transition (EMT), ultimately resulting in radioresistance and recurrence of GC.

scholarly journals Reactive Oxygen Species Regulate T Cell Immune Response in the Tumor Microenvironment

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Xinfeng Chen ◽  
Mengjia Song ◽  
Bin Zhang ◽  
Yi Zhang
Keyword(s):  
Reactive Oxygen Species ◽  
T Cells ◽  
T Cell ◽  
Tumor Microenvironment ◽  
Cancer Treatment ◽  
Reactive Oxygen ◽  
Cell Immune Response ◽  
Oxygen Species ◽  
Cell Based Therapy ◽  
Immunosuppressive Cells

Reactive oxygen species (ROS) produced by cellular metabolism play an important role as signaling messengers in immune system. ROS elevated in the tumor microenvironment are associated with tumor-induced immunosuppression. T cell-based therapy has been recently approved to be effective for cancer treatment. However, T cells often become dysfunctional after reaching the tumor site. It has been reported that ROS participate extensively in T cells activation, apoptosis, and hyporesponsiveness. The sensitivity of T cells to ROS varies among different subsets. ROS can be regulated by cytokines, amino acid metabolism, and enzymatic activity. Immunosuppressive cells accumulate in the tumor microenvironment and induce apoptosis and functional suppression of T cells by producing ROS. Thus, modulating the level of ROS may be important to prolong survival of T cells and enhance their antitumor function. Combining T cell-based therapy with antioxidant treatment such as administration of ROS scavenger should be considered as a promising strategy in cancer treatment, aiming to improve antitumor T cells immunity.

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