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Therapeutical efficacy of gold nanoparticles to glioblastoma multiform or septic encephalopathy in mice

Abstract

Although considered an immunoprivileged organ, the central nervous system (CNS) can still serve as scenario for different diseases. Among the more serious illnesses that affect the CNS are glioblastoma multiform and septic encephalopathy. These diseases own common features, mainly: inflammation and oxidative stress. Nanoparticles has come out as a new strategy for targeting diseases. As one of several properties of the nanoparticles, their reduced size allow them to cross biological membranes, such as the blood brain barrier (BBB). This way, nanoparticles can be efficient transporters for drugs used to treat CNS diseases, but which cannot easily cross the BBB. Among the nanoparticles, the gold ones (AuNPs) own intrinsic properties, they are anti-inflammatory and anti-antioxidant; then, we aim to study the effect of AuNPs treatment in mice with glioblastoma multiform or septic encephalopathy. Glioblastoma multiform will be induced in mice after injection of glioblastoma cells, particularly the GL261 cell line, into the brain parenchyma. Using a different group of mice, septic encephalopathy will be induced using the cecal ligation puncture procedure. Animals will be intravenously (IV) treated with AuNPs covered with citrate, bioconjugated or not with an non-specific antibody (IgG) (10 powered to 12 particles/mL, 20 or 46 nm of average diameter and zeta potential of -10 or -26 mV, for AuNP-cit or AuNP-IgG, respectively, and dispersed in distilled water) or saline, on alternate days, for 20 days, beginning 8 days after the tumor induction; or in a single shot, 2 or 4 hours after induction of sepsis. The following parameters will be measured 28 days after induction of tumor or 6 hours after sepsis: BBB permeability, thrombus formation in cerebral microvessels, cytokines and eicosanoids in the brain parenchyma, number of blood leukocytes and platelets, and markers of pletelet activation/coagulation. Some additional parameters will be determined for each specific disease: tumor volume and expression of tumor markers, and, in sepsis, number of leukocyte and platelet adhesion in cerebral microvessels. Those experiments will be complemented by in vitro assays, using glial tumor cells (GL261) and glial non-tumor cells (BV2), in presence or not of lipopolysaccharide (LPS): growth curve, number of cells in apoptosis and/or necrosis, cell cycle, inflammatory cytokines, reactive oxygen species (ROS) levels, phagocytose by glial cells, and endocytosis of the nanoparticles. (AU)

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
JESUS DA SILVA, VIVIANE DE CASSIA; SILVA, RENEE DE NAZARE O.; COLLI, LUCAS GIGLIO; CATELLI DE CARVALHO, MARIA HELENA; RODRIGUES, STEPHEN FERNANDES. Gold nanoparticles carrying or not anti-VEGF antibody do not change glioblastoma multiforme tumor progression in mice. HELIYON, v. 6, n. 11, . (15/04281-0, 18/12368-6, 14/05146-6)
RODRIGUES, STEPHEN F.; FIEL, LUANA A.; SHIMADA, ANA L.; PEREIRA, NATALIA R.; GUTERRES, SILVIA S.; POHLMANN, ADRIANA R.; FARSKY, SANDRA H.. Lipid-Core Nanocapsules Act as a Drug Shuttle Through the Blood Brain Barrier and Reduce Glioblastoma After Intravenous or Oral Administration. JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, v. 12, n. 5, p. 986-1000, . (11/02438-8, 14/05146-6, 12/02994-0, 11/19595-9)

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