| Summary: | Background: In recent years, magnetic nanoparticles (NMP) as novel materials have been widely used for biomedical, diagnostic and therapeutic purposes like microbial infection therapy. The purpose of this study is to synthesize PO coated iron oxide magnetic nanoparticles (Fe3O4@PO NPs) and their anti-leishmanial effects in vitro and in vivo against cutaneous leishmaniasis. Methods: Fe3O4 magnetic nanoparticles were synthesized by the coprecipitation of Fe2 + and Fe3 + ions and used as a nanocarrier for the production of Fe3O4@PO NPs. The in vitro antileishmanial effects of PO-coated Fe3O4 NPs and Fe3O4 NPs (10–200 µg/mL) was determined against the intracellular amastigotes of Leishmania major (MRHO/IR/75/ER) and, then, examined on cutaneous leishmaniasis induced in male BALB/c mice by L. major. The rate of infectivity, production of nitric oxide (NO), and cytotoxic activates of Fe3O4 NPs and Fe3O4@PO NPs on J774-A1 macrophage cells were determined. Results: The size scattering of the Fe3O4 NPs and Fe3O4@PO NPs were in the range among 1–40 and 5–55 nm, respectively. The obtained IC50 values were 62.3 ± 2.15 μg/mL, 31.3 ± 2.26 μg/mL, and 52.6 ± 2.15 μg/mL for the Fe3O4 NPs and Fe3O4@PO NPs, and MA, respectively. The results revealed that the mean number of parasites and the mean diameter of the lesions was considerably (p < 0.05) decreased in the infected mice treated with Fe3O4 NPs and Fe3O4@PO NPs. The Fe3O4 NPs and Fe3O4@PO NPs significantly (p < 0.05) prompted the production of NO as a dose-dependent manner. The promastigotes pre-incubated in Fe3O4 NPs and Fe3O4@PO NPs at the concentration of 5 µg/mL had the ability to infect only 41.7% and 28.3% of the macrophages cells. The selectivity index of greater than 10 for Fe3O4 NPs and Fe3O4@PO NPs showed its safety to the J774-A1 macrophage cells and specificity to the parasite. Conclusion: The results of this survey indicated the high potency of Fe3O4@PO NPs to inhibit the growth of amastigote forms of L. major as well as recovery and improvement CL induced by L. major in BALB/c mice without significant cytotoxicity. The results also indicated that, although the possible anti-leishmanial mechanisms of Fe3O4@PO NPs have not been clearly understood, however, the triggering of NO may be considered as one of the possible anti-leishmanial mechanisms of these nanoparticles. However, additional studies, in particular in clinical contexts, are mandatory.
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