Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis

Tian, Bo; Li, Fangyuan; Li, Ruiqing; Hu, Xi; Lai, Tianwen; Lu, Jingxiong; Zhao, Yun; Du, Yang; Liang, Zeyu; Zhu, Chen; Shao, Wei; Li, Wen; Chen, Zhihua; Sun, Xiaolian; Chen, Xiaoyuan; Ying, Songmin; Ling, Daishun; Shen, Huahao

doi:10.1016/j.biomaterials.2018.06.020

Cited by 24 publications

(15 citation statements)

References 40 publications

(43 reference statements)

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“…Notably, nano Bcl-2 inhibitor, Nf-ABT-199 could deliver ABT-199 specifically to mitochondria of bronchitis cells, which was proved to significantly reduce airway inflammation and inhibit inflammatory cell infiltration and mucus excessive secretion by effectively inducing eosinophil apoptosis. In addition, Nf-ABT-199 had no significant effect on cell vitality, airway epithelial barrier, and liver function, indicating non-toxicity and good biocompatibility ( 109 ).…”

Section: Therapeutic Drugs Targeting Eosinophilsmentioning

confidence: 99%

Recent advances of eosinophils and its correlated diseases

Zhang¹,

Zhu

Zhang

et al. 2022

Front. Public Health

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Eosinophils are differentiated by bone marrow multipotent progenitor cells and are further released into peripheral blood after maturation. Human eosinophils can exhibit unique multi-leaf nuclear morphology, which are filled with cytoplasmic granules that contain cytotoxicity and immune regulatory proteins. In recent years, many studies focused on the origin, differentiation and development process of eosinophils. It has been discovered that the eosinophils have the regulatory functions of innate and adaptive immunity, and can also function in several diseases, including asthma, chronic obstructive pulmonary diseases, acute respiratory distress syndrome, malignant tumors and so on. Hence, the role and effects of eosinophils in various diseases are emphasized. In this review, we comprehensively summarized the development and differentiation process of eosinophils, the research progress of their related cytokines, diseases and current clinical treatment options, and discussed the potential drug target, aiming to provide a theoretical and practical basis for the clinical prevention and treatment of eosinophil-related diseases, especially respiratory diseases. To conclude, the guiding significance of future disease treatment is proposed based on the recent updated understandings into the cell functions of eosinophils.

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Section: Therapeutic Drugs Targeting Eosinophilsmentioning

confidence: 99%

Recent advances of eosinophils and its correlated diseases

Zhang¹,

Zhu

Zhang

et al. 2022

Front. Public Health

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“…3,[12][13][14] Among them, mitochondria-targeting nanoparticles (NPs) emerged as potential therapeutic alternations due to their improved cell targeting capabilities, desired biodistribution, and better biocompatibilities. [15][16][17] Despite the growing evidence of therapeutic outcomes by inducing mitochondrialmediated tumor cell apoptosis, 2,18 the application of nanodevices on the maintenance of mitochondrial homeostasis was quite limited. TPP-conjugated ceria (TPP-ceria) NPs have been developed to mitigate amyloid beta-induced mitochondrial morphology damage and excessive oxidative stress, thus providing potential therapeutic candidate for Alzheimer's disease.…”

Section: Introductionmentioning

confidence: 99%

<p>Mitochondria-Modulating Porous Se@SiO<sub>2</sub> Nanoparticles Provide Resistance to Oxidative Injury in Airway Epithelial Cells: Implications for Acute Lung Injury</p>

Wang¹,

Wang²,

Deng³

et al. 2020

IJN

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Background: Mitochondrial dysfunction played a vital role in the pathogenesis of various diseases, including acute lung injury (ALI). However, few strategies targeting mitochondria were developed in treating ALI. Recently, we fabricated a porous Se@SiO 2 nanoparticles (NPs) with antioxidant properties. Methods: The protective effect of Se@SiO 2 NPs was assessed using confocal imaging, immunoblotting, RNA-seq, mitochondrial respiratory chain (MRC) activity assay, and transmission electron microscopy (TEM) in airway epithelial cell line (Beas-2B). The in vivo efficacy of Se@SiO 2 NPs was evaluated in a lipopolysaccharide (LPS)-induced ALI mouse model. Results: This study demonstrated that Se@SiO 2 NPs significantly increased the resistance of airway epithelial cells under oxidative injury and shifted lipopolysaccharide-induced gene expression profile closer to the untreated controls. The cytoprotection of Se@SiO 2 was found to be achieved by maintaining mitochondrial function, activity, and dynamics. In an animal model of ALI, pretreated with the NPs improved mitochondrial dysfunction, thus reducing inflammatory responses and diffuse damage in lung tissues. Additionally, RNA-seq analysis provided evidence for the broad modulatory activity of our Se@SiO 2 NPs in various metabolic disorders and inflammatory diseases. Conclusion: This study brought new insights into mitochondria-targeting bioactive NPs, with application potential in curing ALI or other human mitochondria-related disorders.

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“…Reproduced with permission. [ 139 ] Copyright 2019, Elsevier. C) The image (C1 and C2) and histogram (C3) of 19 F/ 1 H magnetic resonance angiography about house dust mite (HDM) rats treated with α v β 3 ‐No drug micelles and α v β 3 ‐DXTL‐PD micelles.…”

Section: Respiratory Injuries and Disease Treatment With Nanomedicinesmentioning

confidence: 99%

“…The nanomedicine specifically delivered ABT‐199 to the mitochondria of bronchial inflammatory cells, thereby inducing apoptosis of inflammatory cells to inhibit airway inflammation and airway hyper‐responsiveness. [ 139 ] As shown in Figure 12B, nanoformulated Bcl‐2 inhibitor ABT‐199 (Nf‐ABT‐199) were able to accumulate in the mitochondria of inflammatory cells and effectively alleviate airway inflammation by inducing eosinophil apoptosis, inhibiting inflammatory cell infiltration and mucus over‐secretion.…”

Section: Respiratory Injuries and Disease Treatment With Nanomedicinesmentioning

confidence: 99%

Nanomedicines Targeting Respiratory Injuries for Pulmonary Disease Management

Liu

Long

Gao

et al. 2022

Adv Funct Materials

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The respiratory system holds crucial importance in the biology of vertebrate animals. Injuries of the respiratory system caused by viral infections (e.g., by COVID‐19, MERS, and SARS) can lead to severe or lethal conditions. So far there are no effective treatments for respiratory injuries. This represents a highly unmet clinical need, e.g., during the current COVID‐19 pandemic. Nanomedicines have high potential in the treatment of respiratory injuries. In this review, the pathology and clinical treatments of major respiratory injuries, acute lung injury, and acute respiratory distress syndrome are briefly summarized. The review primarily focuses on nanomedicines based on liposomes, solid lipid nanoparticles, polymeric nanoparticles, and inorganic nanoparticles, which are tested in preclinical models for the treatment of respiratory injuries. These nanomedicines are utilized to deliver a variety of therapeutic agents, including corticosteroids, statins, and nucleic acids. Furthermore, nanomedicines are also investigated for other respiratory diseases including chronic obstructive pulmonary disease and asthma. The promising preclinical results of various nanoformulations from these studies suggest the potential of nanomedicines for future clinical management of respiratory viral infections and diseases.

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Nanoformulated ABT-199 to effectively target Bcl-2 at mitochondrial membrane alleviates airway inflammation by inducing apoptosis

Cited by 24 publications

References 40 publications

Recent advances of eosinophils and its correlated diseases

Recent advances of eosinophils and its correlated diseases

<p>Mitochondria-Modulating Porous Se@SiO<sub>2</sub> Nanoparticles Provide Resistance to Oxidative Injury in Airway Epithelial Cells: Implications for Acute Lung Injury</p>

Nanomedicines Targeting Respiratory Injuries for Pulmonary Disease Management

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