Fe3O4@Bio-MOF Nanoparticles Combined with Artemisinin, Glucantime®, or Shark Cartilage Extract on Iranian Strain of Leishmania major (MRHO/IR/75/ER): An In-Vitro and In-Vivo Study

BACKGROUND: In the present study, we examined the effects of Fe3O4@bio-MOF nanoparticle (Nano-FO) plus artemisinin (Art) and glucantime (Glu) or shark cartilage extract (ShCE) on Leishmania major in vitro and in vivo. METHODS: This experimental study was conducted at the laboratory of Department of Parasitology, Tarbiat Modares University, Tehran, Iran during 2016–2017. The promastigote and amastigote assays were performed were conducted at the presence of 3.12–400 μg/mL of the drug combinations. According to in vitro IC50 results, the combinations of 12.5μg/mL Nano-FO with 25 μg/mL Art as well as 200 μg/mL Glu and 0.5 mL of 20 mg/kg of ShCE were used to treat BALB/c mice. During and at the end of the treatment, the lesion sizes were measured. Parasite loads, cytokine levels were evaluated at the end of the treatment. RESULTS: The IC(50) of Fe(3)O(4)@bio-MOF-Artemisinin (Nano-FO/Art), Fe(3)O(4)@bio-MOF-Glucantime (Nano-FO/Glu), and Fe(3)O(4)@bio-MOF-Shark cartilage extract (Nano-FO/ShCE) on promasitigotes were 12.58±0.12, 235±0.17, and 18.54±0.15, respectively. These results on amastigotes were 10.32±0.01, 187±0.03, and 338±0.07 μg/mL, respectively. The apoptosis percentage of these combinations were 32.54%, 20.59%, and 15.68% in promastigotes and 15.68%, 12.84%, and 3.51% in infected macrophages, respectively with no toxicity on uninfected macrophages. In vivo results showed that the size of lesions significantly decreased against all drugs combinations, but Nano-FO/Art combination with Selectivity Index of 23.62 value was safe, and more effective on healing of lesions than other drugs combinations (P=0.003). CONCLUSION: This study suggested that Nano-FO/Art combination can be considered as an anti-leishmania combination therapy in CL induced by L. major.