DNase I functional microgels for neutrophil extracellular trap disruption

Hosseinnejad, Aisa; Ludwig, Nadine; Wienkamp, Ann-Katrin; Rimal, Rahul; Berne, Christian; Rossaint, Rolf; Rossaint, Jan; Singh, Smriti

doi:10.1039/d1bm01591e

Cited by 36 publications

(25 citation statements)

References 84 publications

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“…[ 17 ] This includes the display or release of inhibitors of coagulation factors and antiplatelet agents, release of nitric oxide and digestion of neutrophil extracellular trap, and display of thrombolytic agents. [ 18 ] In spite of the improved hemocompatibility, passive as well as active coatings fail to completely inhibit surface‐induced coagulation. On the one hand, passive antifouling coatings fail as soon as very small amounts of coagulation factors manage to adsorb and self‐amplification mechanisms becomes activated resulting in the propagation of coagulation and clot formation.…”

Section: Introductionmentioning

confidence: 99%

Interactive Hemocompatible Nanocoating to Prevent Surface‐Induced Coagulation in Medical Devices

Quandt

Garay‐Sarmiento

Witzdam

et al. 2022

Adv Materials Inter

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Interfacing blood with any artificial surface instantly triggers the activation of coagulation at the interface, posing a risk of adverse thromboembolic complications. Immediately upon contact, blood proteins adsorb to the surface turning it into an active prothrombogenic and proinflammatory interface promoting the activation of platelets and the coagulation cascade. Here, an interactive hemocompatible nanocoating is designed that synergistically combines antifouling polymer brushes with the activity of an anti‐FXIIa antibody to tackle the two main causes of surface‐induced coagulation. The brushes provide a passive layer rendering the surface stealth and non‐thrombogenic against blood activation. Furthermore, as soon as traces of FXIIa arise, the coating immediately and specifically scavenges it, thus actively switching‐off contact activation right at the beginning. Moreover, a means is developed to translate this coating to a broad range of polymeric surfaces commonly used in medical devices. The coated surfaces prevent protein adsorption and provide a barrier to bacterial colonization while being capable of capturing biologically relevant concentrations of FXIIa. Notably, the coating completely prevents the formation of clots on the surface when exposed to blood. Thus, the interactive anti‐FXIIa nanocoating provides a new avenue to improve the hemocompatibility of medical devices in a safe and efficient manner.

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Section: Introductionmentioning

confidence: 99%

Interactive Hemocompatible Nanocoating to Prevent Surface‐Induced Coagulation in Medical Devices

Quandt

Garay‐Sarmiento

Witzdam

et al. 2022

Adv Materials Inter

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show abstract

“…Recent studies that focused on patients with ARDS secondary to COVID-19 found that aerosolized pulmozyme had positive effects in relieving acute respiratory failure and improving patients’ outcomes [ 28 , 29 ]. However, rh-DNase I was metabolized rapidly, whereas the pulmonary inflammation was persistent, which made it difficult for therapeutic effects to be maintained for a long time [ 29 , 30 ]. Thus, novel therapies targeting NETs-related DNA might be a promising treatment.…”

Section: Discussionmentioning

confidence: 99%

NETs Promote Inflammatory Injury by Activating cGAS-STING Pathway in Acute Lung Injury

Zhao

Zhen

Zhou

et al. 2023

IJMS

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Acute respiratory distress syndrome (ARDS) threatens the survival of critically ill patients, the mechanisms of which are still unclear. Neutrophil extracellular traps (NETs) released by activated neutrophils play a critical role in inflammatory injury. We investigated the role of NETs and the underlying mechanism involved in acute lung injury (ALI). We found a higher expression of NETs and cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) in the airways, which was reduced by Deoxyribonuclease I (DNase I) in ALI. The administration of the STING inhibitor H-151 also significantly relieved inflammatory lung injury, but failed to affect the high expression of NETs in ALI. We isolated murine neutrophils from bone marrow and acquired human neutrophils by inducing HL-60 to differentiate. After the PMA interventions, exogenous NETs were obtained from such extracted neutrophils. Exogenous NETs intervention in vitro and in vivo resulted in airway injury, and such inflammatory lung injury was reversed upon degrading NETs with or inhibiting cGAS-STING with H-151 as well as siRNA STING. In conclusion, cGAS-STING participates in regulating NETs-mediated inflammatory pulmonary injury, which is expected to be a new therapeutic target for ARDS/ALI.

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“…Several works which are under experimental research or preclinically used include degrading already formed NETs and blocking the aberrant formation of NETs (shown in Table 3). DNase I is one of the endonucleases that cleave DNA, resulting in the collapse of the web-like structure, and is commonly used as a NETs inhibitor [140]. Previous studies reported that Dnase I could improve diabetic wound healing through the clearance of NETs [141] and mechanistically research revealed that Dnase I exerted its function mainly by improving inflammation resolution, reactivating epithelial regeneration-related signaling pathways, and attenuating the cumulation of reactive oxygen species (ROS) [142].…”

Section: Potential Treatment Strategies For Inhibiting Netsmentioning

confidence: 99%

Neutrophil extracellular traps primed intercellular communication in cancer progression as a promising therapeutic target

et al. 2023

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In addition to the anti-infection response, neutrophils are linked to tumor progression through the secretion of inflammation components and neutrophil extracellular traps (NETs) formation. NET is a web-like structure constituted by a chromatin scaffold coated with specific nuclear and cytoplasmic proteins, such as histone and granule peptides. Increasing evidence has demonstrated that NETs are favorable factors to promote tumor growth, invasion, migration, and immunosuppression. However, the cell–cell interaction between NETs and other cells (tumor cells and immune cells) is complicated and poorly studied. This work is the first review to focus on the intercellular communication mediated by NETs in cancer. We summarized the complex cell–cell interaction between NETs and other cells in the tumor microenvironment. We also address the significance of NETs as both prognostic/predictive biomarkers and molecular targets for cancer therapy. Moreover, we presented a comprehensive landscape of cancer immunity, improving the therapeutic efficacy for advanced cancer in the future.

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DNase I functional microgels for neutrophil extracellular trap disruption

Abstract: Non-fouling DNase I conjugated microgel provide a novel biohybrid platform to disrupt Neutrophil extracellular traps (NETs) and can be used as a non-thrombogenic coating for reduction of NET-mediated inflammation and microthrombi formation.

Cited by 36 publications

References 84 publications

Interactive Hemocompatible Nanocoating to Prevent Surface‐Induced Coagulation in Medical Devices

Interactive Hemocompatible Nanocoating to Prevent Surface‐Induced Coagulation in Medical Devices

NETs Promote Inflammatory Injury by Activating cGAS-STING Pathway in Acute Lung Injury

Neutrophil extracellular traps primed intercellular communication in cancer progression as a promising therapeutic target

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