Beta‐1,3‐D‐glucan nanoparticle mediated delivery of siRNAs to professional phagocytes for inhibiting Leishmania infection

Abstract

Nanoparticle‐based delivery systems represent a new paradigm for drug design. Many pathogenic diseases, such as leishmaniasis, can be efficiently treated by localized, macrophage‐targeted therapies. The parasitic protozoan Leishmania invades mammalian macrophages to establish infection. We reported previously that Leishmania manipulates the expression of several non‐coding RNA genes (e.g., Alu RNA, B1 RNA and SRP RNA) in the macrophages to favor the establishment of their infection in the phagolysosomes of these cells (Ueda Y., and Chaudhuri, G. J. Biol. Chem. 275, 19428, 2000; Misra, S., Tripathi, M. K., and Chaudhuri, G. J. Biol. Chem. 280, 29364, 2005). Our recent data suggests that Leishmania exposure to the macrophages leads to the decrease in several ncRNA levels including various miRNAs. Replenishment of these RNAs in macrophages can make them relatively resistant to Leishmania infection. Here we report the use of hollow yeast cell wall particles (YCWPs) caging the above ncRNAs for delivery to macrophages in order to make them resistant to Leishmania infection. Our findings support the idea that YCWPs mediated delivery to macrophages can beused to replenish RNA or knock down specific genes within these cells to exert therapeutic effects against Leishmaniasis. Supported by NIH NIAID grants R01AI042327 and R21AI076757 to GC.