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

• Grant number: 15/05148-1
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2015
• End date: December 01, 2018
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
• Principal Investigator: Marcio José Tiera
• Grantee: Maicon Segalla Petrônio
• Company: Dnapta Biotecnologia Ltda
• Associated scholarship(s): 17/04392-1 - Synthesis and characterization of bioresponsive nanodevices for site-targeted release of siRNA for treatment of rheumatoid arthritis, BE.EP.PD

Abstract

This project aims to build efficient and site-specific nanodevices to the transport and release of siRNA for the development of an alternative treatment for rheumatoid arthritis. The proposal is based on previous in vitro results, obtained with nanoparticles prepared with biocompatible derivatives of chitosan (CH). The adjustment of composition provided an efficient intracellular release of interfering RNA (siRNA), effectively silencing expression of messenger RNA in different cell types. The stability of the nanostructure under physiological conditions, as well as the efficient intracellular release are the challenges of this project. Thus, structural changes will be performed to increase the efficiency, biocompatibility and stability of the nanodevices, followed by in vivo studies. The decreasing pH of the endosomal compartment, and the presence the disulfide bridges within the nanodevices will be explored to facilitate the intracellular release. Nanodevices will be tested in vitro and in vivo in an arthritis model induced by collagen. The project is linked to two ongoing projects (PVE-CNPq nº. 407499/2013-0, FAPESP-PIPE 14 / 50198-4/Dnapta Biotechnology Ltda). (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)

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)

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)