Synthesis and characterization of bioresponsive nanodevices for site-targeted release of siRNA for treatment of rheumatoid arthritis

• Grant number: 17/04392-1
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: September 01, 2017
• End date: March 01, 2018
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Marcio José Tiera
• Grantee: Maicon Segalla Petrônio
• Supervisor: Julio Cesar Fernandes
• Institution abroad: Université de Montréal, Canada
• Associated to the scholarship: 15/05148-1 - Synthesis and characterization of bioresponsives nanodevices for site-targeted release of siRNA for treatment of rheumatoid arthritis, BP.PD

Abstract

The first part of this project was dedicated to the synthesis and characterization of new derivatives of chitosan, focusing the improvement of the stability and buffering capacity of the nanoparticles. Derivatives were synthesized (CH-DEAE15-PEG, QO-DEAE9 and QDDEAE50) and characterized by 1H NMR, FTIR and gel permeation chromatography. The improvement of nanoparticle's stability was conceived by conjugation of poly(ethylene glycol) via a disulfide linkage, aiming to improve its disassembling into the reductive environment of the endosome. Nanoparticles with the pEGFP plasmid and siRNA-TNF-± were prepared and characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The obtained nanoparticles exhibited improved colloidal stability and had diameters ranging from 50 nm to 300 nm. The cytotoxicities of the polymers were evaluated on L929 fibroblast cell line and the cell viabilities remained above 80%. Nanoparticles prepared with both derivatives (CH-DEAE15, CH-DEAE15-PEG) induced only mild (~5%) hemolysis on human erythrocytes at highest concentration utilized (2.0 g.L-1). Based on these results, the next step of the project is to perform the in vitro and in vivo studies using these nanoparticles. The in vitro study will be performed by focusing the knockdown of tumor necrosis factor (TNF) alpha (TNF-±) and the receptor activator of nuclear factor kappa ² ligand. In vivo studies will be performed using the arthritis inflammation model induced in mice with type II anti-collagen monoclonal antibody. (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)

RONDON, ELSA PATRICIA; BENABDOUN, HOUDA ABIR; VALLIERES, FRANCIS; PETRONIO, MAICON SEGALLA; TIERA, MARCIO JOSE; BENDERDOUR, MOHAMED; FERNANDES, JULIO CESAR. Evidence Supporting the Safety of Pegylated Diethylaminoethyl-Chitosan Polymer as a Nanovector for Gene Therapy Applications. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 15, p. 18-pg., 2020-01-01. (15/05148-1, 17/10331-5, 17/04392-1)