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

Grant number: 14/05146-6
Support type:Research Grants - Young Investigators Grants
Duration: May 01, 2015 - April 30, 2019
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Stephen Fernandes de Paula Rodrigues
Grantee:Stephen Fernandes de Paula Rodrigues
Home Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Assoc. researchers:Eliana Hiromi Akamine ; Maria Helena Catelli de Carvalho
Associated scholarship(s):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, BP.IC
18/12368-6 - Kinesis of a fluorescently labelled gold nanoparticle through the blood brain barrier of mice, in vivo, and in the murine glioblastoma cell line, GL261, BP.IC
17/01762-2 - Effect of treatment with gold nanoparticles on protein expression of oxidative and inflammatory markers in mice brain or blood cells with sepsis-associated encephalopathy and glioblastoma multiforme, BP.IC
16/18602-5 - Therapeutic efficacy of gold nanoparticles in septic encephalopathy in mice, BP.IC
15/04281-0 - Therapeutical efficacy of gold nanoparticles to multiform glioblastoma or septic encephalophaty in mice, BP.JP

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)

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)
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, MAY 2016. Web of Science Citations: 28.

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