Gold nanoparticles reduce inflammation in cerebral microvessels of mice with sepsis

Author(s)

Di Bella, Davide ^[1] ; Ferreira, Joao P. S. ^[1] ; Silva, Renee de Nazare O. ^[1] ; Echem, Cinthya ^[1] ; Milan, Aline ^[1] ; Akamine, Eliana H. ^[1] ; Carvalho, Maria H. ^[1] ; Rodrigues, Stephen F. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Hypertens Diabet & Vasc Biol, Ave Prof Lineu Prestes 1524, ICB 1, Sala 205, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Lab Vasc Nanopharmacol, Ave Prof Lineu Prestes 1524, ICB 1, Sala 319, BR-05508900 Sao Paulo - Brazil

• Document type: Journal article
• Source: JOURNAL OF NANOBIOTECHNOLOGY; v. 19, n. 1 FEB 19 2021.
• Web of Science Citations: 1

Abstract

Background: Sepsis is an emergency medical condition that can lead to death and it is defined as a life-threatening organ dysfunction caused by immune dysregulation in response to an infection. It is considered the main killer in intensive care units. Sepsis associated-encephalopathy (SAE) is mostly caused by a sepsis-induced systemic inflammatory response. Studies report SAE in 14-63% of septic patients. Main SAE symptoms are not specific and usually include acute impairment of consciousness, delirium and/or coma, along with electroencephalogram (EEG) changes. For those who recover from sepsis and SAE, impaired cognitive function, mobility and quality of life are often observed months to years after hospital discharge, and there is no treatment available today to prevent that. Inflammation and oxidative stress are key players for the SAE pathophysiology. Gold nanoparticles have been demonstrated to own important anti-inflammatory properties. It was also reported 20 nm citrate-covered gold nanoparticles (cit-AuNP) reduce oxidative stress. In this context, we tested whether 20 nm cit-AuNP could alleviate the acute changes caused by sepsis in brain of mice, with focus on inflammation. Sepsis was induced in female C57BL/6 mice by cecal ligation and puncture (CLP), 20 nm cit-AuNP or saline were intravenously (IV) injected 2 h after induction of sepsis and experiments performed 6 h after induction. Intravital microscopy was used for leukocyte and platelet adhesion study in brain, blood brain barrier (BBB) permeability carried out by Evans blue assay, cytokines measured by ELISA and real time PCR, cell adhesion molecules (CAMs) by flow cytometry and immunohistochemistry, and transcription factors, by western blotting. Results: 20 nm cit-AuNP treatment reduced leukocyte and platelet adhesion to cerebral blood vessels, prevented BBB failure, reduced TNF- concentration in brain, and ICAM-1 expression both in circulating polymorphonuclear (PMN) leukocytes and cerebral blood vessels of mice with sepsis. Furthermore, 20 nm cit-AuNP did not interfere with the antibiotic effect on the survival rate of mice with sepsis. Conclusions: Cit-AuNP showed important anti-inflammatory properties in the brain of mice with sepsis, being a potential candidate to be used as adjuvant drug along with antibiotics in the treatment of sepsis to avoid SAE (AU)

• FAPESP's process: 16/18602-5 - Therapeutic efficacy of gold nanoparticles in septic encephalopathy in mice
• Grantee: Davide Di Bella
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• FAPESP's process: 15/04281-0 - Therapeutical efficacy of gold nanoparticles to multiform glioblastoma or septic encephalophaty in mice
• Grantee: Stephen Fernandes de Paula Rodrigues
• Support Opportunities: Scholarships in Brazil - Young Researchers
• FAPESP's process: 18/12258-6 - Effect of gold nanoparticles treatment on the acute expression of inflammatory transcription factors and on the chronic expression of excitatory neurotransmiters in brain of sepsis encephalophaty-induced mice
• Grantee: João Paulo de Sousa Ferreira
• Support Opportunities: Scholarships in Brazil - Scientific Initiation