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Development of chitosomes' nanoparticles for modulation of inflammation and angiogenesis by dual delivery: an approach to gene therapy for limb ischemia

Grant number: 20/06913-1
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2020
Effective date (End): July 31, 2023
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Sang Won Han
Grantee:Bianca Bonetto Moreno Garcia
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Associated research grant:15/20206-8 - Modulation of monocytes, macrophages and pericytes by the colony stimulating factor genes to treat murine limb ischemia, AP.TEM

Abstract

Peripheral arterial disease is characterized by the narrowing of peripheral vessels, and can advance to Critical Limb Ischemia (CLI). Within a year, 25% of patients die and 30% suffer amputation due to the lack of therapeutic options. The two main pathophysiological changes that occur in ischemic tissue are the decrease in blood flow and the increase in inflammation, which need to be addressed in the therapeutic elaboration. miR-93 is a member of the miRNA 106b ~ 25 cluster that acts on the regulation of VEGF and IL-8 expression, cell proliferation and migration, cell cycle and tube formation, while the Macrophage Colony Stimulating Factor (M-CSF) leads to the polarization of type M2 anti-inflammatory macrophages. Thus, an approach using M-CSF and miR-93 could lead to a better recovery of CLI. However, due to the rapid degradation of nucleic acids in the organism, the use of gene carriers becomes essential. In our previous work, we developed a new carrier called chitosome that was made by complexing modified chitosan with arginine plus liposome made with DOPE/DOTAP. In HEK293T cells, the transfection efficiency was H90%. In this context, the present project aims to improve the chitosome nanoparticles as a dual delivery platform, for the delivery of the DNA encoding M-CSF and miR-93 for the treatment of limb ischemia. (AU)