Abstract
The treatment of cutaneous leishmaniasis (CL) is challenged by limited therapeutic options, high drug toxicity, and frequent treatment failure. In this context, iron oxide nanoparticles (IONPs) have emerged as promising therapeutic alternatives. This review summarizes experimental findings on the in vitro and in vivo anti-Leishmania activity of IONPs, highlighting their potential as a treatment for CL. A systematic search of PubMed, ScienceDirect, and Scopus identified 16 studies evaluating the anti-Leishmania effects of IONPs across various CL models. The studies assessed IONPs' physicochemical properties (size, shape, polydispersity index, and zeta potential), functionalization strategies, and efficacy against axenic and intracellular Leishmania forms, as well as in animal models. Most studies investigated spherical IONPs ranging from 5 to 90 nm, with polydispersity index values between 0.2 and 1.0 and zeta potentials from -13 mV to +35 mV. Functionalization improved dispersion and enabled antimicrobial conjugation. IONPs reduced axenic Leishmania viability, decreased intracellular parasitism, and lowered parasite loads in infected mouse lesions. In vitro, parasite death was linked to lysosomal rupture, oxidative stress, apoptosis, necrosis, and nitric oxide production by macrophages. In vivo, treated animals exhibited reduced parasite burdens, milder lesions, and enhanced IFN-γ production, suggesting improved immune responses. Despite these promising effects, issues such as formulation optimization, biocompatibility, and evaluation of pharmacokinetics and pharmacodynamics remain to be addressed. IONPs represent a novel and promising dual-action therapeutic strategy for CL, combining antiparasitic effects with immune modulation. However, important knowledge gaps persist regarding their mechanisms of action, long-term safety, efficacy across different Leishmania species and clinical scenarios. Further research is needed to advance IONPs as a safe and effective treatment for CL.