Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages

Research output: Contribution to journalArticle

Roberto Molinaro, Anna Pastò, Claudia Corbo, Francesca Taraballi, Federica Giordano, Jonathan O. Martinez, Picheng Zhao, Xin Wang, Assaf Zinger, Christian Boada, Kelly A. Hartman, Ennio Tasciotti

Despite numerous advances in medical treatment, sepsis remains one of the leading causes of death worldwide. Sepsis is characterized by the involvement of all organs and tissues as a consequence of blood poisoning, resulting in organ failure and eventually death. Effective treatment remains an unmet need and novel approaches are urgently needed. The growing evidence of clinical and biological heterogeneity of sepsis suggests precision medicine as a possible key for achieving therapeutic breakthroughs. In this scenario, biomimetic nanomedicine represents a promising avenue for the treatment of inflammatory diseases, including sepsis. We investigated the role of macrophage-derived biomimetic nanoparticles, namely leukosomes, in a lipopolysaccharide-induced murine model of sepsis. We observed that treatment with leukosomes was associated with significantly prolonged survival. In vitro studies elucidated the potential mechanism of action of these biomimetic vesicles. The direct treatment of endothelial cells (ECs) with leukosomes did not alter the gene expression profile of EC-associated cell adhesion molecules. In contrast, the interaction of leukosomes with macrophages induced a decrease of pro-inflammatory genes (IL-6, IL-1b, and TNF-α), an increase of anti-inflammatory ones (IL-10 and TGF-β), and indirectly an anti-inflammatory response on ECs. Taken together, these results showed the ability of leukosomes to regulate the inflammatory response in target cells, acting as a bioactive nanotherapeutic.

Original languageEnglish (US)
Pages (from-to)13576-13586
Number of pages11
JournalNanoscale
Volume11
Issue number28
DOIs
StatePublished - Jul 28 2019

PMID: 31290914

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Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages. / Molinaro, Roberto; Pastò, Anna; Corbo, Claudia; Taraballi, Francesca; Giordano, Federica; Martinez, Jonathan O.; Zhao, Picheng; Wang, Xin; Zinger, Assaf; Boada, Christian; Hartman, Kelly A.; Tasciotti, Ennio.

In: Nanoscale, Vol. 11, No. 28, 28.07.2019, p. 13576-13586.

Research output: Contribution to journalArticle

Harvard

Molinaro, R, Pastò, A, Corbo, C, Taraballi, F, Giordano, F, Martinez, JO, Zhao, P, Wang, X, Zinger, A, Boada, C, Hartman, KA & Tasciotti, E 2019, 'Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages' Nanoscale, vol. 11, no. 28, pp. 13576-13586. https://doi.org/10.1039/c9nr04253a

APA

Molinaro, R., Pastò, A., Corbo, C., Taraballi, F., Giordano, F., Martinez, J. O., ... Tasciotti, E. (2019). Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages. Nanoscale, 11(28), 13576-13586. https://doi.org/10.1039/c9nr04253a

Vancouver

Molinaro R, Pastò A, Corbo C, Taraballi F, Giordano F, Martinez JO et al. Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages. Nanoscale. 2019 Jul 28;11(28):13576-13586. https://doi.org/10.1039/c9nr04253a

Author

Molinaro, Roberto ; Pastò, Anna ; Corbo, Claudia ; Taraballi, Francesca ; Giordano, Federica ; Martinez, Jonathan O. ; Zhao, Picheng ; Wang, Xin ; Zinger, Assaf ; Boada, Christian ; Hartman, Kelly A. ; Tasciotti, Ennio. / Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages. In: Nanoscale. 2019 ; Vol. 11, No. 28. pp. 13576-13586.

BibTeX

@article{e95011f1d722401cb0a71aa4369194c8,
title = "Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages",
abstract = "Despite numerous advances in medical treatment, sepsis remains one of the leading causes of death worldwide. Sepsis is characterized by the involvement of all organs and tissues as a consequence of blood poisoning, resulting in organ failure and eventually death. Effective treatment remains an unmet need and novel approaches are urgently needed. The growing evidence of clinical and biological heterogeneity of sepsis suggests precision medicine as a possible key for achieving therapeutic breakthroughs. In this scenario, biomimetic nanomedicine represents a promising avenue for the treatment of inflammatory diseases, including sepsis. We investigated the role of macrophage-derived biomimetic nanoparticles, namely leukosomes, in a lipopolysaccharide-induced murine model of sepsis. We observed that treatment with leukosomes was associated with significantly prolonged survival. In vitro studies elucidated the potential mechanism of action of these biomimetic vesicles. The direct treatment of endothelial cells (ECs) with leukosomes did not alter the gene expression profile of EC-associated cell adhesion molecules. In contrast, the interaction of leukosomes with macrophages induced a decrease of pro-inflammatory genes (IL-6, IL-1b, and TNF-α), an increase of anti-inflammatory ones (IL-10 and TGF-β), and indirectly an anti-inflammatory response on ECs. Taken together, these results showed the ability of leukosomes to regulate the inflammatory response in target cells, acting as a bioactive nanotherapeutic.",
author = "Roberto Molinaro and Anna Past{\`o} and Claudia Corbo and Francesca Taraballi and Federica Giordano and Martinez, {Jonathan O.} and Picheng Zhao and Xin Wang and Assaf Zinger and Christian Boada and Hartman, {Kelly A.} and Ennio Tasciotti",
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journal = "Nanoscale",
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publisher = "Royal Society of Chemistry",
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RIS

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T1 - Macrophage-derived nanovesicles exert intrinsic anti-inflammatory properties and prolong survival in sepsis through a direct interaction with macrophages

AU - Molinaro, Roberto

AU - Pastò, Anna

AU - Corbo, Claudia

AU - Taraballi, Francesca

AU - Giordano, Federica

AU - Martinez, Jonathan O.

AU - Zhao, Picheng

AU - Wang, Xin

AU - Zinger, Assaf

AU - Boada, Christian

AU - Hartman, Kelly A.

AU - Tasciotti, Ennio

PY - 2019/7/28

Y1 - 2019/7/28

N2 - Despite numerous advances in medical treatment, sepsis remains one of the leading causes of death worldwide. Sepsis is characterized by the involvement of all organs and tissues as a consequence of blood poisoning, resulting in organ failure and eventually death. Effective treatment remains an unmet need and novel approaches are urgently needed. The growing evidence of clinical and biological heterogeneity of sepsis suggests precision medicine as a possible key for achieving therapeutic breakthroughs. In this scenario, biomimetic nanomedicine represents a promising avenue for the treatment of inflammatory diseases, including sepsis. We investigated the role of macrophage-derived biomimetic nanoparticles, namely leukosomes, in a lipopolysaccharide-induced murine model of sepsis. We observed that treatment with leukosomes was associated with significantly prolonged survival. In vitro studies elucidated the potential mechanism of action of these biomimetic vesicles. The direct treatment of endothelial cells (ECs) with leukosomes did not alter the gene expression profile of EC-associated cell adhesion molecules. In contrast, the interaction of leukosomes with macrophages induced a decrease of pro-inflammatory genes (IL-6, IL-1b, and TNF-α), an increase of anti-inflammatory ones (IL-10 and TGF-β), and indirectly an anti-inflammatory response on ECs. Taken together, these results showed the ability of leukosomes to regulate the inflammatory response in target cells, acting as a bioactive nanotherapeutic.

AB - Despite numerous advances in medical treatment, sepsis remains one of the leading causes of death worldwide. Sepsis is characterized by the involvement of all organs and tissues as a consequence of blood poisoning, resulting in organ failure and eventually death. Effective treatment remains an unmet need and novel approaches are urgently needed. The growing evidence of clinical and biological heterogeneity of sepsis suggests precision medicine as a possible key for achieving therapeutic breakthroughs. In this scenario, biomimetic nanomedicine represents a promising avenue for the treatment of inflammatory diseases, including sepsis. We investigated the role of macrophage-derived biomimetic nanoparticles, namely leukosomes, in a lipopolysaccharide-induced murine model of sepsis. We observed that treatment with leukosomes was associated with significantly prolonged survival. In vitro studies elucidated the potential mechanism of action of these biomimetic vesicles. The direct treatment of endothelial cells (ECs) with leukosomes did not alter the gene expression profile of EC-associated cell adhesion molecules. In contrast, the interaction of leukosomes with macrophages induced a decrease of pro-inflammatory genes (IL-6, IL-1b, and TNF-α), an increase of anti-inflammatory ones (IL-10 and TGF-β), and indirectly an anti-inflammatory response on ECs. Taken together, these results showed the ability of leukosomes to regulate the inflammatory response in target cells, acting as a bioactive nanotherapeutic.

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DO - 10.1039/c9nr04253a

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