Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury
Abstract Acute lung injury (ALI) is characterized by severe inflammation in lung tissue, excessive immune response and impaired lung function. In hospitalized high-risk patients and cases of secondary infection due to surgical contamination, it can lead to higher mortality rates and require immediat...
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| Format: | Article |
| Language: | English |
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SpringerOpen
2025-02-01
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| Series: | Nano Convergence |
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| Online Access: | https://doi.org/10.1186/s40580-025-00475-4 |
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| author | Jungbum Kim Donghyuk Seo So-Yeol Yoo Hye-Jin Lee Jisun Kim Ji Eun Yeom Jae-Young Lee Wooram Park Kyung Soo Hong Wonhwa Lee |
| author_facet | Jungbum Kim Donghyuk Seo So-Yeol Yoo Hye-Jin Lee Jisun Kim Ji Eun Yeom Jae-Young Lee Wooram Park Kyung Soo Hong Wonhwa Lee |
| author_sort | Jungbum Kim |
| collection | DOAJ |
| description | Abstract Acute lung injury (ALI) is characterized by severe inflammation in lung tissue, excessive immune response and impaired lung function. In hospitalized high-risk patients and cases of secondary infection due to surgical contamination, it can lead to higher mortality rates and require immediate intervention. Currently, clinical treatments are limited in symptomatic therapy as mechanical ventilation and corticosteroids, having insufficient efficacy in mitigating the cause of progression to severe illness. Here we report a pulmonary targeting lung-homing nanoliposome (LHN) designed to attenuate excessive Neutrophil Extracellular Trap formation (NETosis) through sivelestat and DNase-1, coupled with an anti-inflammatory effect mediated by 25-hydroxycholesterol (25-HC), offering a promising intervention for the acute phase of ALI. Through intratracheal delivery, we intend prompt and constant action within the lungs to effectively prevent excessive NETosis. Isolated neutrophils from blood samples of severe ARDS patients demonstrated significant anti-NETosis effects, as well as reduced proinflammatory cytokine secretion. Furthermore, in a murine model of LPS-induced ALI, we confirmed improvements in lung histopathology, and early respiratory function. Also, attenuation of systemic inflammatory response syndrome (SIRS), with notable reductions in NETosis and neutrophil trafficking was investigated. This presents a targeted therapeutic approach that can be applied in early stages of high-risk patients to prevent severe pulmonary disease progression. |
| format | Article |
| id | doaj-art-6a6a82b744cf410ba3b86c70d6d6208e |
| institution | Kabale University |
| issn | 2196-5404 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Nano Convergence |
| spelling | doaj-art-6a6a82b744cf410ba3b86c70d6d6208e2025-02-09T12:49:49ZengSpringerOpenNano Convergence2196-54042025-02-0112111710.1186/s40580-025-00475-4Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injuryJungbum Kim0Donghyuk Seo1So-Yeol Yoo2Hye-Jin Lee3Jisun Kim4Ji Eun Yeom5Jae-Young Lee6Wooram Park7Kyung Soo Hong8Wonhwa Lee9Department of Chemistry, Sungkyunkwan UniversityDepartment of Chemistry, Sungkyunkwan UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityDepartment of Chemistry, Sungkyunkwan UniversityDepartment of Chemistry, Sungkyunkwan UniversityDepartment of Chemistry, Sungkyunkwan UniversityCollege of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National UniversityDepartment of Integrative Biotechnology, College of Biotechnology and Bioengineering, Sungkyunkwan UniversityDivision of Pulmonology and Allergy, Department of Internal Medicine, College of Medicine, Regional Center for Respiratory Diseases, Yeungnam University, Yeungnam University Medical CenterDepartment of Chemistry, Sungkyunkwan UniversityAbstract Acute lung injury (ALI) is characterized by severe inflammation in lung tissue, excessive immune response and impaired lung function. In hospitalized high-risk patients and cases of secondary infection due to surgical contamination, it can lead to higher mortality rates and require immediate intervention. Currently, clinical treatments are limited in symptomatic therapy as mechanical ventilation and corticosteroids, having insufficient efficacy in mitigating the cause of progression to severe illness. Here we report a pulmonary targeting lung-homing nanoliposome (LHN) designed to attenuate excessive Neutrophil Extracellular Trap formation (NETosis) through sivelestat and DNase-1, coupled with an anti-inflammatory effect mediated by 25-hydroxycholesterol (25-HC), offering a promising intervention for the acute phase of ALI. Through intratracheal delivery, we intend prompt and constant action within the lungs to effectively prevent excessive NETosis. Isolated neutrophils from blood samples of severe ARDS patients demonstrated significant anti-NETosis effects, as well as reduced proinflammatory cytokine secretion. Furthermore, in a murine model of LPS-induced ALI, we confirmed improvements in lung histopathology, and early respiratory function. Also, attenuation of systemic inflammatory response syndrome (SIRS), with notable reductions in NETosis and neutrophil trafficking was investigated. This presents a targeted therapeutic approach that can be applied in early stages of high-risk patients to prevent severe pulmonary disease progression.https://doi.org/10.1186/s40580-025-00475-4Lung-homing nanoliposomeNETosisAcute respiratory distress syndrome (ARDS)DNase-1Sivelestat |
| spellingShingle | Jungbum Kim Donghyuk Seo So-Yeol Yoo Hye-Jin Lee Jisun Kim Ji Eun Yeom Jae-Young Lee Wooram Park Kyung Soo Hong Wonhwa Lee Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury Nano Convergence Lung-homing nanoliposome NETosis Acute respiratory distress syndrome (ARDS) DNase-1 Sivelestat |
| title | Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury |
| title_full | Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury |
| title_fullStr | Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury |
| title_full_unstemmed | Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury |
| title_short | Lung-homing nanoliposomes for early intervention in NETosis and inflammation during acute lung injury |
| title_sort | lung homing nanoliposomes for early intervention in netosis and inflammation during acute lung injury |
| topic | Lung-homing nanoliposome NETosis Acute respiratory distress syndrome (ARDS) DNase-1 Sivelestat |
| url | https://doi.org/10.1186/s40580-025-00475-4 |
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