Journal
ACTA BIOMATERIALIA
Volume 148, Issue -, Pages 258-270Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.actbio.2022.06.024
Keywords
Dexamethasone; ROS-responsive polymers; Nanoparticles; Acute lung injury; LPS-induced
Funding
- Natural Science Foundation of Zhejiang Province [LD21E030 0 01]
- National Natural Science Foundation of China [51873188]
- Stem Cell and Translational Research , National Key Research and Development Program of China [2020YFA0113003]
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Acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, and there is an urgent need for medication and effective drug delivery to reduce inflammation. The study found that PFTU@DEX NPs can effectively suppress inflammatory cells, ROS signaling pathways, and cell apoptosis to ameliorate ALI.
The acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, which activates various reactive oxygen species (ROS) signaling pathways and causes severe complications in patients as currently seen in coronavirus disease 2019 (COVID-19). There is an urgent need for medication of the inflammatory lung environment and effective delivery of drugs to lung to reduce the burden of high doses of medications and attenuate inflammatory cells and pathways. Herein, we prepared dexamethasone-loaded ROS-responsive polymer nanoparticles (PFTU@DEX NPs) by a modified emulsion approach, which achieved high loading content of DEX (11.61 %). DEX was released faster from the PFTU@DEX NPs in a ROS environment, which could scavenge excessive ROS efficiently both in vitro and in vivo. The PFTU NPs and PFTU@DEX NPs showed no hemolysis and cytotoxicity. Free DEX, PFTU NPs and PFTU@DEX NPs shifted Ml macrophages to M2 macrophages in RAW264.7 cells, and showed anti-inflammatory modulation to A549 cells in vitro. The PFTU@DEX NPs treatment significantly reduced the increased total protein concentration in BALF of ALI mice. The delivery of PFTU@DEX NPs decreased the proportion of neutrophils significantly, mitigated the cell apoptosis remarkably compared to the other groups, reduced Ml macrophages and increased M2 macrophages in vivo. Moreover, the PFTU@DEX NPs had the strongest ability to suppress the expression of NLRP3, Caspasel, and IL-1 beta. Therefore, the PFTU@DEX NPs could efficiently suppress inflammatory cells, ROS signaling pathways, and cell apoptosis to ameliorate LPS-induced ALI. Statement of Significance The acute lung injury (ALI) is an inflammatory disorder associated with cytokine storm, which activates various reactive oxygen species (ROS) signaling pathways and causes severe complications in patients. There is an urgent need for medication of the inflammatory lung environment and effective delivery of drugs to modulate the inflammatory disorder and suppress the expression of ROS and inflammatory cytokines. The inhaled PFTU@DEX NPs prepared through a modified nanoemulsification method suppressed the activation of NLRP3, induced the polarization of macrophage phenotype from M1 to M2, and thereby reduced the neutrophil infiltration, inhibited the release of proteins and inflammatory mediators, and thus decreased the acute lung injury in vivo. (C) 2022 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.
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