MiR-155-chitosan polyplex as a novel therapeutic modality against Leishmania major: A feasibility study

Leishmaniasis is a neglected tropical disease affecting millions of people worldwide. Macrophages play a crucial role in the life cycle of Leishmania and host-parasite interactions. Leishmania parasites have evolved mechanisms to modulate macrophage miRNA, including miR-155, in order to evade immune responses. Modulation of miR-155 levels could potentially restore balanced immune responses while enhancing the host's ability to clear parasites.

This study aims to evaluate the antileishmanial effects of the miR-155 chitosan polyplex (miR-155 CP) in vitro.

The antileishmanial activity of miR-155 CP synthesized by the coacervation method was assessed against Leishmania major by analyzing the IL-12 and IL-10 secretion, nitric oxide (NO) and urea production, as well as cell death rate on infected RAW 264.7 cells in vitro.

The polyplexes were produced with high transfection efficiency. MiR-155 was up-regulated over 20-fold in healthy macrophages and 6-fold among infected macrophages. The mean cell death index among treated infected cells (65.5 ± 4.5) increased significantly compared to the infected control group (25±5). Treatment with miR-155 CP triggered the production of IL-12 and NO among uninfected and infected macrophages.

Collectively, our findings suggest that induction of miR-155 expression via miR-155 CP may influence cellular mechanisms in two ways: eliminating infected macrophages and enabling uninfected ones to manage the parasite.