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Evaluation of the therapeutic potential of superparamagnetic iron oxide nanoparticles containing gold in rats with rheumatoid arthritis

Grant number: 14/06744-4
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): October 01, 2014
Effective date (End): September 30, 2016
Field of knowledge:Health Sciences - Pharmacy - Toxicological Analysis
Acordo de Cooperação: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Fernando Barbosa Júnior
Grantee:Maria Fernanda Hornos Carneiro
Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


Rheumatoid arthritis (RA) is a systemic, autoimmune and incurable chronic inflammatory disease affecting synovial tissues causing pain, stiffness and inflammation. Medications containing metal gold (Au) have shown good results in improving symptoms of RA. However, due to the high toxicity of the metal and its wide tissue distribution, several side effects are observed during treatment. More recently, nanomaterials have been gaining significant attention, mainly for their physicochemical characteristics that confer more potent action and consequent reduction of dose, in addition to its potential use allied to intelligent systems - that can both control the release of nanomaterials and/or direct them to the target. In this proposal, we intend to evaluate the therapeutic potential of Au nanoparticles linked to superparamagnetic iron oxide nanoparticles (SPIONs) - in mice with collagen-induced AR. After administration of SPIONs containing Au nanoparticles to animals, Au will be directed to the injured tissue by the application of an external magnetic field (neodymium magnet). For this purpose, adult male Wistar rats will be divided into the following treatment groups (n = 6/group): 1) negative controls (without inducing AR), 2) positive controls (induction with RA, treatment with SPIONS without Au) 3) SPIONs containing Au, 4) colloidal Au nanoparticles and 5) Methotrexate (0.1 mg / kg). In order to verify decreased symptomatology, several parameters will be evaluated, such as concentration of cytokines (IL-1 and IL-6 and TNF-±) and leukocyte count in the synovial lavage, measuring edema, liver enzymes in serum, redox state (levels of F2-isoprostanes, total glutathione, glutathione peroxidase and catalase activities), Au distribution in tissues (liver, kidney and spleen), histopathological assessment of joint tissue and analysis of genotoxicity (micronucleus and comet). Regarding AR, the present study has an important role, since the proposed therapy (Au nanoparticles linked to SPIONs and its focus in the injured tissue through neodymium magnet) consists of a simple and practical methodology, and potentially effective. Also, it is a potential way to strongly minimize the side effects- so prevalent in the conventional therapy of RA - since there will be focus and targeting of the therapeutic agent to the affected region, something never before accomplished in RA. Thus, the presently proposed therapy could be easily adapted for use in humans - after ethical procedures and required tests - which would allow increased quality of life for individuals affected by RA. (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)
HORNOS CARNEIRO, MARIA FERNANDA; MACHADO, ANA RITA T.; ANTUNES, LUSANIA M. G.; SOUZA, TALITA E.; FREITAS, VICTOR A.; OLIVEIRA, LUIZ C. A.; RODRIGUES, JAIRO L.; PEREIRA, MARCIO C.; BARBOSA, FERNANDO. Gold-Coated Superparamagnetic Iron Oxide Nanoparticles Attenuate Collagen-Induced Arthritis after Magnetic Targeting. BIOLOGICAL TRACE ELEMENT RESEARCH, v. 194, n. 2, p. 502-513, . (14/06744-4)
AZEVEDO, LARA FERREIRA; KARPOVA, NINA; ROCHA, BRUNO ALVES; BARBOSA JR, FERNANDO; GOBE, GLENDA CAROLYN; CARNEIRO, MARIA FERNANDA HORNOS. Evidence on Neurotoxicity after Intrauterine and Childhood Exposure to Organomercurials. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH, v. 20, n. 2, p. 19-pg., . (16/10456-0, 18/24069-3, 18/19554-0, 16/07661-0, 14/06744-4)

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