AMF-responsive nanobiomagnetite for targeted delivery of amphotericin B against Leishmania amazonensis

Cutaneous leishmaniasis remains a neglected tropical disease with limited treatment options. Available therapies include costly and toxic drugs for which recurrent cases of resistance are reported. Drug delivery systems based on the association of approved drugs and nanoparticles have improved pharmacological properties of the drug, such as targeted therapy, enhanced drug solubility, reduced side effects, and potentially lower doses required for effective treatment. In this study, we explored the in vitro potential use of the nanobiomagnetite produced by magnetotactic bacteria functionalized with amphotericin B against promastigotes of Leishmania amazonensis, one of the main pathogens of cutaneous leishmaniasis. Additionally, the antileishmanial activity of the nanoformulation was significantly increased in association with alternating magnetic field (AMF) exposure, indicating an advantage in the therapeutic efficacy of the drug, potentially leading to a combined therapy. In addition, to assess the preliminary safety of the nanoformulation, we assessed its cytotoxicity on HaCaT, hFB, and J774.16 cell lines; none of the tested nanoformulations were cytotoxic toward these cell lines, suggesting their potential for biocompatible therapeutic applications. Moreover, no significant nitric oxide production was detected with the nanoparticle's interaction on J774.16 macrophages. This finding is vital for further clinical considerations, as it reduces the risk of inflammatory responses. Thus, we demonstrated the biocompatibility and parasitic potential of functionalized nanobiomagnetite as an alternative AMF-responsive therapy in in vitro models. However, in vivo testing is still necessary to assess the nanoformulation activity against Leishmania.