Sustainable Nanosheet Antioxidants for Sepsis Therapy via Scavenging Intracellular Reactive Oxygen and Nitrogen Species
- 7 August 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in ACS Nano
- Vol. 14 (8), 10324-10336
- https://doi.org/10.1021/acsnano.0c03807
Abstract
Sepsis is an aberrant systemic inflammatory response mediated by excessive production of reactive oxygen species (ROS) and reactive nitrogen species (RNS). Developing an efficient antioxidant therapy for sepsis via scavenging ROS and RNS remains a big challenge owing to insufficient activity and sustainability of conventional antioxidants. Herein, biocompatible transition metal dichalcogenide antioxidants with excellent scavenging activity and sustainability for H2O2, O2•-, OH• and nitric oxide are developed for effective sepsis treatment. WS2, MoSe2, and WSe2 nanosheets exfoliated and functionalized with a biocompatible polymer effectively scavenge mitochondrial and intracellular ROS and RNS in inflammatory cells. Among the nanosheets, WS2 most efficiently suppresses the excessive secretion of inflammatory cytokines along with scavenging ROS and RNS without affecting the expression levels of the anti-inflammatory cytokine and ROS-producing enzymes. The WS2 nanosheets significantly improve the survival rate up to 90% for severely septic mice by reducing systemic inflammation. The pharmacokinetics suggests that the WS2 nanosheets can be excreted from mice three days after intravenous injection. This work demonstrates the potential of therapeutic nanosheet antioxidants for effective treatment of ROS and RNS-related diseases.Keywords
Funding Information
- Korea Health Industry Development Institute (HP20C0006)
- National Research Foundation of Korea (2017R1A2B2008455, 2019R1I1A2A01064237)
This publication has 79 references indexed in Scilit:
- Liquid Exfoliation of Layered MaterialsScience, 2013
- Identification of individual and few layers of WS2 using Raman SpectroscopyScientific Reports, 2013
- Photoluminescence emission and Raman response of monolayer MoS_2, MoSe_2, and WSe_2Optics Express, 2013
- Bench-to-bedside review: Sepsis - from the redox point of viewCritical Care, 2011
- Harmful molecular mechanisms in sepsisNature Reviews Immunology, 2008
- Rare earth nanoparticles prevent retinal degeneration induced by intracellular peroxidesNature Nanotechnology, 2006
- Reactive oxygen species as mediators of organ dysfunction caused by sepsis, acute respiratory distress syndrome, or hemorrhagic shock: potential benefits of resuscitation with Ringerʼs ethyl pyruvate solutionCurrent Opinion in Clinical Nutrition and Metabolic Care, 2002
- Terephthalic acid: A dosimeter for the detection of hydroxyl radicals in vitroLife Sciences, 1994
- Free radicals and antioxidants in sepsisCritical Care Medicine, 1993
- X-ray photoemission study of oxygen and nitric oxide adsorption on MoS2Journal of Catalysis, 1986