Nanocarriers for siRNA Delivery: Synthesis e Selection of Vectors for the Treatment of Inflammatory Diseases.

• Grant number: 17/10331-5
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2017
• End date: April 30, 2020
• Field of knowledge: Interdisciplinary Subjects
• Principal Investigator: Marcio José Tiera
• Grantee: Marcio José Tiera
• Host Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil
• Associated researchers: Aline Margarete Furuyama Lima ; Julio Cesar Fernandes ; Maicon Segalla Petrônio ; Sang Won Han ; Vera Aparecida de Oliveira Tiera

Abstract

Nowadays, the development of alternative therapies for the treatment of inflammatory diseases is an urgent need due to the high cost and limitation of the traditional treatments. In this subject the gene therapy via delivery of small interfering RNA is a promising approach when targeted to modulate the macrophages response, since they play major roles in many chronic diseases including atherosclerosis, inflammatory bowel disease and rheumatoid arthritis. These diseases have a great financial impact on the public health system due to high cost of the treatments that employ monoclonal antibodies. We have recently shown that nanoparticles prepared using chitosan derivatives provided an in vitro knockdown of about 90% of the mRNA (targeted mRNA). The invention was financed by projects from FAPESP (2011/13960-0; PIPE 2014 / 50198-4) and CNPq (PVE- 407499 / 2013-0) and resulted in a patent deposit (process number BR 10 2016 030231 5) having as co-applicant the Université de Montréal-Canada.This project aims to optimize the structure and stability of the nanoparticles to achieve an efficient in vivo delivery. The project involves a first step of synthesis and preparation of nanoparticles focusing the treatment of limb ischemia and rheumatoid arthritis. Aiming at the treatment of rheumatoid arthritis, the nanoparticles will be tested in vitro for the silencing of TNF-alpha in macrophages through the use of interfering RNA (siRNA-TNF-alpha). siRNA loaded nanoparticles will be also targeted to promote the knockdown of the CCR2 chemokine found in circulating inflammatory monocytes. By using this strategy we intend to increase the non-inflammatory monocytes (Ly6Clow) and accordingly to improve the population of the M2 pro-resolutive macrophages. (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)

MARTINS, GRAZIELI OLINDA; PETRONIO, MAICON SEGALLA; FURUYAMA LIMA, ALINE MARGARETE; MARTINEZ JUNIOR, ANDRE MIGUEL; DE OLIVEIRA TIERA, VERA APARECIDA; CALMON, MARILIA DE FREITAS; LEITE VILAMAIOR, PATRICIA SIMONE; HAN, SANG WON; TIERA, MARCIO JOSE. Amphipathic chitosans improve the physicochemical properties of siRNA-chitosan nanoparticles at physiological conditions. Carbohydrate Polymers, v. 216, p. 332-342, JUL 15 2019. (17/10331-5, 12/24259-0, 15/05148-1, 15/20206-8)

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)

MARTINEZ JUNIOR, ANDRE MIGUEL; FELIX VIEGAS DE SOUZA, RICCHARD HALLAN; PETRONIO, MAICON SEGALLA; MARTINS, GRAZIELI OLINDA; FERNANDES, JULIO CESAR; BENDERDOUR, MOHAMED; OLIVEIRA DE TIERA, VERA APARECIDA; TIERA, MARCIO JOSE. Double-grafted chitosans as siRNA nanocarriers: effects of diisopropylethylamine substitution and labile-PEG coating. JOURNAL OF NANOSTRUCTURE IN CHEMISTRY, v. N/A, p. 20-pg., 2022-03-31. (17/10331-5, 19/27801-0, 15/05148-1, 09/53989-4)