Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm

Kim, Hyelim; Lee, Han Sol; Ahn, Jae‐Jun; Hong, Kyung Soo; Jang, Jong Geol; An, Jiseon; Mun, Yong-Hyeon; Yoo, So‐Yeol; Choi, Yoon Jung; Yun, Mi Young; Song, Gyu Yong; Joo, Jinmyoung; Na, Dong Hee; Kim, Hong Nam; Park, Hee Ho; Lee, Jae-Young; Lee, Wonhwa

doi:10.1016/j.nantod.2021.101149

Cited by 25 publications

(28 citation statements)

References 47 publications

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“…Therapeutics that selectively target the lungs have tremendous potential in managing COVID-19 as SARS-CoV-2 invades via lung ACE2 receptors causing severe pneumonia. Recent reports have confirmed the association between 25-hydroxycholesterol and cytokine levels [148][149][150]. The activation of inflammatory SREBP2-and NF-κB-mediated inflammasome signaling pathways play a major role in COVID-19 pathogenesis.…”

Section: Immunomodulatory and Immunotherapeutic Approaches To Counter Cytokine Stormmentioning

confidence: 79%

“…The activation of inflammatory SREBP2- and NF-κB-mediated inflammasome signaling pathways play a major role in COVID-19 pathogenesis. Therefore, 25-hydroxycholesterol and di-dodecyl dimethylammonium bromide nanovesicles can be considered as potential drug candidates that restore the intracellular cholesterol level, thereby inhibiting cytokine storm [ 150 , 151 ]. The findings indicate that 25-hydroxycholesterol and di-dodecyl dimethylammonium can downregulate NF-κB and SREBP2 signaling pathways.…”

Section: Immunomodulatory and Immunotherapeutic Approaches To Counter Cytokine Stormmentioning

confidence: 99%

“…The findings indicate that 25-hydroxycholesterol and di-dodecyl dimethylammonium can downregulate NF-κB and SREBP2 signaling pathways. Furthermore, they can selectively accumulate in the lung tissues, reducing inflammatory cytokine levels [ 150 ]. Other than standard therapeutic options, numerous molecular intervention approaches are being studied to tackle the cytokine storm, such as targeting the microRNAs that are required for cytokine development.…”

Section: Immunomodulatory and Immunotherapeutic Approaches To Counter Cytokine Stormmentioning

confidence: 99%

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Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

et al. 2021

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The pathogenesis of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still not fully unraveled. Though preventive vaccines and treatment methods are out on the market, a specific cure for the disease has not been discovered. Recent investigations and research studies primarily focus on the immunopathology of the disease. A healthy immune system responds immediately after viral entry, causing immediate viral annihilation and recovery. However, an impaired immune system causes extensive systemic damage due to an unregulated immune response characterized by the hypersecretion of chemokines and cytokines. The elevated levels of cytokine or hypercytokinemia leads to acute respiratory distress syndrome (ARDS) along with multiple organ damage. Moreover, the immune response against SARS-CoV-2 has been linked with race, gender, and age; hence, this viral infection’s outcome differs among the patients. Many therapeutic strategies focusing on immunomodulation have been tested out to assuage the cytokine storm in patients with severe COVID-19. A thorough understanding of the diverse signaling pathways triggered by the SARS-CoV-2 virus is essential before contemplating relief measures. This present review explains the interrelationships of hyperinflammatory response or cytokine storm with organ damage and the disease severity. Furthermore, we have thrown light on the diverse mechanisms and risk factors that influence pathogenesis and the molecular pathways that lead to severe SARS-CoV-2 infection and multiple organ damage. Recognition of altered pathways of a dysregulated immune system can be a loophole to identify potential target markers. Identifying biomarkers in the dysregulated pathway can aid in better clinical management for patients with severe COVID-19 disease. A special focus has also been given to potent inhibitors of proinflammatory cytokines, immunomodulatory and immunotherapeutic options to ameliorate cytokine storm and inflammatory responses in patients affected with COVID-19.

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Section: Immunomodulatory and Immunotherapeutic Approaches To Counter Cytokine Stormmentioning

confidence: 79%

Section: Immunomodulatory and Immunotherapeutic Approaches To Counter Cytokine Stormmentioning

confidence: 99%

Section: Immunomodulatory and Immunotherapeutic Approaches To Counter Cytokine Stormmentioning

confidence: 99%

See 1 more Smart Citation

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

et al. 2021

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“…Similarly, treatment with VX-765 (a caspase-1 inhibitor) suppresses NLRP inflammasome activation and the secretion of IL-1β [ 8 ]. Additionally, the development of nanovesicles through biomedical engineering may prevent the cytokine storm that occurs in patients with COVID-19 [ 60 ]. For instance, 25-hydroxycholesterol and didodecyldimethylammonium bromide (25-HC@DDAB) nanovesicles are lung-specific and with high efficacy [ 60 ].…”

Section: Consideration Of Targeted Therapiesmentioning

confidence: 99%

“…Additionally, the development of nanovesicles through biomedical engineering may prevent the cytokine storm that occurs in patients with COVID-19 [ 60 ]. For instance, 25-hydroxycholesterol and didodecyldimethylammonium bromide (25-HC@DDAB) nanovesicles are lung-specific and with high efficacy [ 60 ]. The 25-HC@DDAB inhibits the cytokine storm in PBMCs derived from patients with COVID-19.…”

Section: Consideration Of Targeted Therapiesmentioning

confidence: 99%

Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

Cheon

Koo

2021

IJMS

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The outbreak of the coronavirus disease 2019 (COVID-19) began at the end of 2019. COVID-19 is caused by infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with COVID-19 may exhibit poor clinical outcomes. Some patients with severe COVID-19 experience cytokine release syndrome (CRS) or a cytokine storm—elevated levels of hyperactivated immune cells—and circulating pro-inflammatory cytokines, including interleukin (IL)-1β and IL-18. This severe inflammatory response can lead to organ damage/failure and even death. The inflammasome is an intracellular immune complex that is responsible for the secretion of IL-1β and IL-18 in various human diseases. Recently, there has been a growing number of studies revealing a link between the inflammasome and COVID-19. Therefore, this article summarizes the current literature regarding the inflammasome complex and COVID-19.

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COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

Zheng,

Li,

et al. 2023

Medicinal Research Reviews

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As severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants continue to wreak havoc worldwide, the “Cytokine Storm” (CS, also known as the inflammatory storm) or Cytokine Release Syndrome has reemerged in the public consciousness. CS is a significant contributor to the deterioration of infected individuals. Therefore, CS control is of great significance for the treatment of critically ill patients and the reduction of mortality rates. With the occurrence of variants, concerns regarding the efficacy of vaccines and antiviral drugs with a broad spectrum have grown. We should make an effort to modernize treatment strategies to address the challenges posed by mutations. Thus, in addition to the requirement for additional clinical data to monitor the long‐term effects of vaccines and broad‐spectrum antiviral drugs, we can use CS as an entry point and therapeutic target to alleviate the severity of the disease in patients. To effectively combat the mutation, new technologies for neutralizing or controlling CS must be developed. In recent years, nanotechnology has been widely applied in the biomedical field, opening up a plethora of opportunities for CS. Here, we put forward the view of cytokine storm as a therapeutic target can be used to treat critically ill patients by expounding the relationship between coronavirus disease 2019 (COVID‐19) and CS and the mechanisms associated with CS. We pay special attention to the representative strategies of nanomaterials in current neutral and CS research, as well as their potential chemical design and principles. We hope that the nanostrategies described in this review provide attractive treatment options for severe and critical COVID‐19 caused by CS.

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Lung-selective 25-hydroxycholesterol nanotherapeutics as a suppressor of COVID-19-associated cytokine storm

Abstract: Graphical Abstract

Cited by 25 publications

References 47 publications

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Diverse Immunological Factors Influencing Pathogenesis in Patients with COVID-19: A Review on Viral Dissemination, Immunotherapeutic Options to Counter Cytokine Storm and Inflammatory Responses

Inflammatory Response in COVID-19 Patients Resulting from the Interaction of the Inflammasome and SARS-CoV-2

COVID‐19 cooling: Nanostrategies targeting cytokine storm for controlling severe and critical symptoms

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