The Tumor Microenvironment: Characterization, Redox Considerations, and Novel Approaches for Reactive Oxygen Species-Targeted Gene Therapy

2013 ◽  
Vol 19 (8) ◽  
pp. 854-895 ◽  
Author(s):  
Lucia Laura Policastro ◽  
Irene Laura Ibañez ◽  
Cintia Notcovich ◽  
Hebe Alicia Duran ◽  
Osvaldo Luis Podhajcer
2020 ◽  
Vol 28 ◽  
Author(s):  
RamaRao Malla ◽  
Mohammad Amjad Kamal

: The breast tumor microenvironment (TME) promotes drug resistance through an elaborated interaction of TME components mediated by reactive oxygen species (ROS). Despite a massive accumulation of data concerning the targeting the ROS, but little is known about the ROS-responsive nanomedicine for targeting breast TME. This review submits the ROS landscape in breast TME, including ROS biology, ROS mediated carcinogenesis, reprogramming of stromal and immune cells of TME. We also discussed ROS-based precision strategies for imaging TME, including molecular imaging techniques with advanced probes, multiplexed methods, and multi-omic profiling strategies. ROS-responsive nanomedicine also describes various therapies, such as chemo-dynamic, photodynamic, photothermal, sono-dynamic, immune, and gene therapy for BC. We expound ROS-responsive primary delivery systems for chemotherapeutics, phytochemicals, and immunotherapeutics. This review also presents recent updates on nano-theranostics for simultaneous diagnosis and treatment of BCs. We assume that review on this advancing field will be beneficial to the development of ROS-based nanotheranostics for BC.


2019 ◽  
Vol 20 (10) ◽  
pp. 2469 ◽  
Author(s):  
Hyeon Joo Yoo ◽  
Yibin Liu ◽  
Lei Wang ◽  
Maria-Luisa Schubert ◽  
Jean-Marc Hoffmann ◽  
...  

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.


RSC Advances ◽  
2019 ◽  
Vol 9 (68) ◽  
pp. 39924-39931 ◽  
Author(s):  
Kecan Lin ◽  
Ziguo Lin ◽  
Yujie Li ◽  
Youshi Zheng ◽  
Da Zhang

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


Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 457 ◽  
Author(s):  
Janina Frisch ◽  
Adrian Angenendt ◽  
Markus Hoth ◽  
Leticia Prates Roma ◽  
Annette Lis

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.


2019 ◽  
Vol 29 (44) ◽  
pp. 1905013 ◽  
Author(s):  
Zhihao Zhao ◽  
Weiqi Wang ◽  
Chenxi Li ◽  
Yiqiu Zhang ◽  
Tianrong Yu ◽  
...  

Nanomedicine ◽  
2021 ◽  
Vol 16 (3) ◽  
pp. 221-235 ◽  
Author(s):  
Ying-kai Tao ◽  
Xiao-yang Hou ◽  
Huan Gao ◽  
Xin Zhang ◽  
Feng-mei Zuo ◽  
...  

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.


2021 ◽  
Vol 9 (39) ◽  
pp. 8253-8262
Author(s):  
Yali Chen ◽  
Yujun Cai ◽  
Xingsu Yu ◽  
Hong Xiao ◽  
Haozhe He ◽  
...  

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.


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