Topical AuNPs-Cys-Sm29 gel modulates the course of lesion development in experimental cutaneous leishmaniasis

The Sm29 antigen from Schistosoma mansoni has been shown to downregulate excessive inflammation associated with immune-mediated diseases. In contrast, cutaneous leishmaniasis (CL) caused by Leishmania (Viannia) braziliensis is marked by an inflammatory response that, when uncontrolled, contributes to disease pathology. In this study, we evaluated the therapeutic potential of topical rSm29 in combination with meglumine antimoniate (Sbv) in experimental murine CL. First, rSm29 was functionalized onto spherical gold nanoparticles using a cysteamine linker (AuNPs-Cys-Sm29). Topical application of this formulation of rSm29 significantly decreased ear lesion thickness, and the combination of topical AuNPs-Cys-Sm29 plus intraperitoneal Sbv also significantly reduced ear lesion thickness, parasite load in the infection site, and the local inflammatory infiltrate when compared to mice treated with Sbv only. The production of IFN-γ, TNF, and IL-10 was reduced in the draining lymph node, as well as the total number of CD3+CD4+IFN+ and CD3+CD4+TNF+ T cells in the infection site. This study demonstrated that combination therapy with topical AuNPs-Cys-Sm29 + systemic Sbv reduced inflammation without compromising parasite clearance. These findings highlight the potential of AuNPs-Cys-Sm29 as a host-directed strategy in treating cutaneous leishmaniasis (CL).