scholarly journals A MXene-Based Bionic Cascaded-Enzyme Nanoreactor for Tumor Phototherapy/Enzyme Dynamic Therapy and Hypoxia-Activated Chemotherapy

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Xiaoge Zhang ◽  
Lili Cheng ◽  
Yao Lu ◽  
Junjie Tang ◽  
Qijun Lv ◽  
...  
Keyword(s):  
Immune Escape ◽  
Membrane Vesicles ◽  
Oxygen Depletion ◽  
Redox Status ◽  
Therapeutic Effects ◽  
Dynamic Therapy ◽  
Additional Chemotherapy ◽  
Anticancer Treatment ◽  
Biomimetic Membrane ◽  
Intracellular Redox Status

AbstractThe enzyme-mediated elevation of reactive oxygen species (ROS) at the tumor sites has become an emerging strategy for regulating intracellular redox status for anticancer treatment. Herein, we proposed a camouflaged bionic cascaded-enzyme nanoreactor based on Ti3C2 nanosheets for combined tumor enzyme dynamic therapy (EDT), phototherapy and deoxygenation-activated chemotherapy. Briefly, glucose oxidase (GOX) and chloroperoxidase (CPO) were chemically conjugated onto Ti3C2 nanosheets, where the deoxygenation-activated drug tirapazamine (TPZ) was also loaded, and the Ti3C2-GOX-CPO/TPZ (TGCT) was embedded into nanosized cancer cell-derived membrane vesicles with high-expressed CD47 (meTGCT). Due to biomimetic membrane camouflage and CD47 overexpression, meTGCT exhibited superior immune escape and homologous targeting capacities, which could effectively enhance the tumor preferential targeting and internalization. Once internalized into tumor cells, the cascade reaction of GOX and CPO could generate HClO for efficient EDT. Simultaneously, additional laser irradiation could accelerate the enzymic-catalytic reaction rate and increase the generation of singlet oxygen (1O2). Furthermore, local hypoxia environment with the oxygen depletion by EDT would activate deoxygenation-sensitive prodrug for additional chemotherapy. Consequently, meTGCT exhibits amplified synergistic therapeutic effects of tumor phototherapy, EDT and chemotherapy for efficient tumor inhibition. This intelligent cascaded-enzyme nanoreactor provides a promising approach to achieve concurrent and significant antitumor therapy.

scholarly journals Redox Buffering Capacity of Nanomaterials as an Index of ROS-based Therapeutics and Toxicity: A Preclinical Animal Study

2021 ◽  
Author(s):  
Aniruddha Adhikari ◽  
Susmita Mondal ◽  
Monojit Das ◽  
Ria Ghosh ◽  
Pritam Biswas ◽  
...  
Keyword(s):  
Therapeutic Index ◽  
Redox Status ◽  
Buffering Capacity ◽  
Engineered Nanoparticles ◽  
Ros Generation ◽  
Cellular Functions ◽  
Physiological Level ◽  
Precise Control ◽  
Preclinical Animal Study ◽  
Intracellular Redox Status

Precise control of intracellular redox status, i.e., maintenance of physiological level of reactive oxygen species (ROS) for mediating normal cellular functions (oxidative eustress) while evading the excess ROS stress (distress) is central to the concept of redox medicine. In this regard, engineered nanoparticles with unique ROS generation, transition, or depletion functions have the potential to be the choice of redox therapeutics. However, it is always challenging to estimate whether ROS-induced intracellular events are beneficial or deleterious to the cell. Here, we propose the concept of redox buffering capacity as a therapeutic index of engineered nanomaterials. As a steady redox state is maintained for normal functioning cells, we hypothesize that the ability of a nanomaterial to preserve this homeostatic condition will dictate its therapeutic efficacy. Additionally, the redox buffering capacity is expected to provide information about the nanoparticle toxicity. Here, using citrate functionalized trimanganese tetroxide nanoparticles (C-Mn3O4 NPs) as a model nanosystem we explored its redox buffering capacity in erythrocytes. Furthermore, we went on to study the chronic toxic effect (if any) of this nanomaterial in animal model in order to co-relate with the experimentally estimated redox buffering capacity. This study could function as a framework for assessing the capability of a nanomaterial as redox medicine (whether maintains eustress or damages by creating distress), thus orienting its application and safety for clinical use.

scholarly journals Pleiotropic Effects of Exosomes as a Therapy for Stroke Recovery

2020 ◽  
Vol 21 (18) ◽  
pp. 6894
Author(s):  
Yuji Ueno ◽  
Kenichiro Hira ◽  
Nobukazu Miyamoto ◽  
Chikage Kijima ◽  
Toshiki Inaba ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Membrane Vesicles ◽  
Recombinant Tissue Plasminogen Activator ◽  
Artery Occlusion ◽  
Outcome Data ◽  
Stroke Recovery ◽  
Therapeutic Effects ◽  
Stroke Survivors ◽  
Axonal Outgrowth ◽  
Inflammatory Reactions

Stroke is the leading cause of disability, and stroke survivors suffer from long-term sequelae even after receiving recombinant tissue plasminogen activator therapy and endovascular intracranial thrombectomy. Increasing evidence suggests that exosomes, nano-sized extracellular membrane vesicles, enhance neurogenesis, angiogenesis, and axonal outgrowth, all the while suppressing inflammatory reactions, thereby enhancing functional recovery after stroke. A systematic literature review to study the association of stroke recovery with exosome therapy was carried out, analyzing species, stroke model, source of exosomes, behavioral analyses, and outcome data, as well as molecular mechanisms. Thirteen studies were included in the present systematic review. In the majority of studies, exosomes derived from mesenchymal stromal cells or stem cells were administered intravenously within 24 h after transient middle cerebral artery occlusion, showing a significant improvement of neurological severity and motor functions. Specific microRNAs and molecules were identified by mechanistic investigations, and their amplification was shown to further enhance therapeutic effects, including neurogenesis, angiogenesis, axonal outgrowth, and synaptogenesis. Overall, this review addresses the current advances in exosome therapy for stroke recovery in preclinical studies, which can hopefully be preparatory steps for the future development of clinical trials involving stroke survivors to improve functional outcomes.

Orchestration of biomimetic membrane coating and nanotherapeutics in personalized anticancer therapy

2021 ◽  
Author(s):  
Xuerui Chen ◽  
Bingbing Liu ◽  
Rongliang Tong ◽  
Lin Zhan ◽  
Xuelian Yin ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Anticancer Therapy ◽  
Coated Nanoparticles ◽  
Anticancer Treatment ◽  
Biomimetic Membrane ◽  
Membrane Coating

Benefiting from the special inherency of natural cells, diverse cell membrane-coated nanoparticles can facilitate personalized anticancer treatment.

scholarly journals Regulation of CD20 expression by radiation-induced changes in intracellular redox status

2008 ◽  
Vol 44 (4) ◽  
pp. 614-623 ◽  
Author(s):  
Damodar Gupta ◽  
Meredith E. Crosby ◽  
Alexandru Almasan ◽  
Roger M. Macklis
Keyword(s):  
Redox Status ◽  
Cd20 Expression ◽  
Radiation Induced ◽  
Induced Changes ◽  
Intracellular Redox Status ◽  
Intracellular Redox

scholarly journals Redox Regulation of Adenovirus-Induced AP-1 Activation by Overexpression of Manganese-Containing Superoxide Dismutase

2002 ◽  
Vol 76 (1) ◽  
pp. 355-363 ◽  
Author(s):  
Hannah J. Zhang ◽  
Victoria J. Drake ◽  
Linjing Xu ◽  
Jianfang Hu ◽  
Frederick E. Domann ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Dna Binding ◽  
Redox Regulation ◽  
Recombinant Adenovirus ◽  
Redox Status ◽  
Binding Activity ◽  
Dna Binding Activity ◽  
Promising Tool ◽  
Gel Shift Assay ◽  
Intracellular Redox Status

ABSTRACT Adenovirus gene therapy is a promising tool in the clinical treatment of many genetic and acquired diseases. However, it has also caused pathogenic effects in organs such as the liver. The redox-sensitive transcription factors AP-1 and NF-κB have been implicated in these effects. To study the mechanisms of adenovirus-mediated AP-1 and NF-κB activation and the possible involvement of oxidative stress in adenovirus transduction, rats were injected with either replication-defective recombinant adenovirus with DNA containing the cytomegalovirus promoter region only (AdCMV), adenovirus containing human manganese-containing superoxide dismutase (MnSOD) cDNA (AdMnSOD), or vehicle. Compared to vehicle and AdCMV transduction, MnSOD gene transfer yielded a fivefold increase in liver MnSOD activity 7 days postinjection. Gel shift assay showed that AdCMV transduction induced DNA binding activity for AP-1 but not NF-κB. MnSOD overexpression abolished this activation. Western blotting analysis of c-Fos and c-Jun suggested that up-regulation of c-fos and c-jun gene expression does not directly contribute to the induction of AP-1 activation. Glutathione/glutathione disulfide ratios were decreased by adenovirus transduction and restored by MnSOD overexpression. The AP-1 binding activity that was induced by AdCMV was decreased by immunoprecipitation of Ref-1 protein. Ref-1 involvement was confirmed by restoration of AP-1 binding activity after the immunoprecipitated Ref-1 protein had been added back. AP-1 DNA binding activity was also elevated in control and AdMnSOD-injected rats after addition of the immunoprecipitated Ref-1 protein. These data indicate that cellular transduction by recombinant adenovirus stimulates AP-1 DNA binding activity. Furthermore, our results suggest that MnSOD overexpression decreases AP-1 DNA binding activity by regulating intracellular redox status, with the possible involvement of Ref-1 in this redox-sensitive pathway.

Redox-based regulation of neural stem cell function and Nrf2

2015 ◽  
Vol 43 (4) ◽  
pp. 627-631 ◽  
Author(s):  
Lalitha Madhavan
Keyword(s):  
Oxidative Stress ◽  
Stress Resistance ◽  
Somatic Mutations ◽  
Cell Function ◽  
Therapeutic Potential ◽  
Redox Status ◽  
Common Theme ◽  
Tissue Microenvironment ◽  
Neural Tissues ◽  
Intracellular Redox Status

Neural stem cells (NSCs) play vital roles in the development and maintenance of brain tissues throughout life. They can also potentially act as powerful sources of regeneration and repair during pathology to replace degenerating cells and counteract deleterious changes in the tissue microenvironment. However, both aging and neurodegeneration involve an up-regulation of processes, such as oxidative stress, inflammation, somatic mutations, and reduction in growth factors in neural tissues, which threaten the robust functioning of NSCs. Nevertheless, recent evidence also indicates that NSCs may possess the intrinsic capability to cope with such stressors in their microenvironment. Whereas the mechanisms governing the responses of NSCs to stress are diverse, a common theme that is emerging suggests that underlying changes in intracellular redox status are crucial. Here we discuss such redox-based regulation of NSCs, particularly in relation to nuclear erythroid factor 2-like 2 (Nrf2), which is a key cellular stress resistance factor, and its implications for successfully harnessing NSC therapeutic potential towards developing cell-based therapeutics for nervous system disorders.

scholarly journals Immunosuppressive Exosomes: A New Approach for Treating Arthritis

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Chenjie Yang ◽  
Paul D. Robbins
Keyword(s):  
Gene Therapy ◽  
Autoimmune Disease ◽  
Current Knowledge ◽  
Cell Communication ◽  
Membrane Vesicles ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
The Usa ◽  
Preclinical And Clinical Studies ◽  
Chronic Autoimmune Disease

Rheumatoid arthritis (RA) is a chronic autoimmune disease and one of the leading causes of disability in the USA. Although certain biological therapies, including protein and antibodies targeting inflammatory factors such as the tumor necrosis factor, are effective in reducing symptoms of RA, these treatments do not reverse disease. Also, although novel gene therapy approaches have shown promise in preclinical and clinical studies to treat RA, it is still unclear whether gene therapy can be readily and safely applied to treat the large number of RA patients. Recently, nanosized, endocytic-derived membrane vesicles “exosomes” were demonstrated to function in cell-to-cell communication and to possess potent immunoregulatory properties. In particular, immunosuppressive DC-derived exosomes and blood plasma- or serum-derived exosomes have shown potent therapeutic effects in animal models of inflammatory and autoimmune disease including RA. This paper discusses the current knowledge on the production, efficacy, mechanism of action, and potential therapeutic use of immunosuppressive exosomes for arthritis therapy.

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