Gold Nanoparticles Reduce Inflammation in Cerebral Microvessels of Septic Mice, But Do Not Alter Tumor Progression in Glioblastoma-Induced Mice

S. Rodrigues, R. Silva, L. Fernandes, D. Di Bella, L. Colli, E. Akamine, M. Carvalho
University of Sao Paulo,
Brazil

Keywords: AuNPs, glioblastoma, septic encephalopathy, C57bl/6 mice, intravital microscopy

Summary:

Gold nanoparticles (AuNPs) have showed intrinsic anti-inflammatory and antioxidant properties (Rodrigues et al., Toxicol Sci., 142:497-507, 2014). Inflammation and oxidative stress are key factors for pathophysiology of septic encephalopathy (Bozza et al., Shock, 39:10-16, 2013), and along with angiogenesis, accumulated mutations, and ischemia, corroborate for glioblastoma multiforme progression (Razavi et al., Front Surg., 3:11, 2016). There is so far no efficient treatment for those conditions. Here, we investigated if two- or four-hour AuNPs-citrate (AuNP-cit) treatment (1.9x10^11 particles/mL), given once, intravenously, to cecum ligation and puncture-induced septic C57Bl/6 mice, reduce cerebral inflammatory parameters. Besides, AuNP-cit was given once every three days, intravenously, beginning eight days after craniotomy for GL261 glioblastoma cell line injection, to C57Bl/6 mice, a model of glioblastoma multiforme, and tumor volume was measured 17 days after treatment started. All protocols were approved by a Care and Use of Experimental Animals Committee (register number: 60/2015E). Six hours after sepsis induction, mice presented increased leukocyte and platelet adhesion to cerebral microvessels, observed by intravital microscopy, and blood brain barrier (BBB) failure, measured by Evans blue parenchymal extravasation. Two and four-hour AuNP-cit treatment restored the leukocyte and platelet adhesion count compared to saline treated-septic mice (Figure), but there was no change on the sepsis induced-BBB failure. Another group of mice was treated with sodium aurothiomalate two hours after sepsis induction, in an antiinflammatory dose (0.7 µg/g body weight), and no change on those parameters was observed. Additionally, we observed AuNP-cit treatment (0.01%) prevented BV2 microglial cell proliferation LPS-induced reduction, in vitro. On the other hand, AuNP-cit chronic treatment did not prevent tumor growth, in vivo, or reduced GL261 cell proliferation, in vitro. Thus, gold nanoparticles do not interfere with glioblastoma progression but reduce inflammation in brain of septic mice. Financial support: FAPESP (2014/05146-6). Figure legend: Cerebral microvessels of sham-operated, saline treated sepsis-induced, and AuNP-cit treated sepsis-induced C57Bl/6 mice. Treatment was performed intravenously two hours after sepsis induction. Orange arrows point adhesion leukocytes. Dashed lines highlight blood vessels contour. White bar = 50 µm.