Antimycobacterial activity of Clonostachys rogersoniana MGK33 functionalized metal-coated magnetic nanoparticles

Tuberculosis (TB) drug discovery studies are essential for the discovery of new anti-tubercular agents. TB drugs currently in use are susceptible to resistance by Mycobacterium tuberculosis, hence the need for novel classes of drugs. In this study, mono- and modified bimetallic magnetic iron oxide nanoparticles (MIONs) were investigated for potential use as anti-TB agents. The surfaces of chemically synthesized MIONs were modified with Ni, Zn, Au, Cu and Ag, to form bi-metallic NPs. High-resolution transmission electron microscopy (HRTEM) results showed that the diameter of the NPs was in the range of 20–32 nm. Magnetic measurements showed that NPs exhibited saturation magnetization measured of 76.18 emu/g for mono-metallic MIONs, 42.89 emu/g for Zn-MIONs, 52.74 emu/g for Au-MIONs, 57.93 emu/g for Cu-MIONs and 62.96 emu/g for Ag-MIONs. Thereafter, mono- and bimetallic MIONs were functionalized with a crude fungal extract from Clonostachys rogersoniana MGK33. Evidence of functionalization was confirmed by liquid chromatography mass spectrometry (LCMS) analysis. In particular, extraction efficiency of bionectin F by the nanoparticles was calculated and found to be highest for Ni-MIONs@MGK33 (22.94 %). Extracellular antimycobacterial assays against Mycobacterium smegmatis mc2155 showed that the Cu-MIONs and Ag-MIONs had the strongest activity, exhibiting total growth inhibition at concentrations as low as 15.63 and 7.81 µg/mL respectively. Functionalized Cu-MIONs@MGK33 and Ag-MIONs@MGK33 exhibited weaker activity, leading to the assumption that the adsorbed metabolites reduced the bioactive surface area of the nanoparticles and thus limited contact with targets. Cu-MIONs and Ag-MIONs were found to be non-cytotoxic to RAW 264.7 macrophage cells at concentrations of 1.96 and 3.91 µg/mL, while Cu-MIONs were able induce higher levels of late apoptosis in M. smegmatis mc2155 infected RAW 264.7 macrophage cells, compared to Cu-MIONs@MGK33, Ag-MIONs and Ag-MIONs@MGK33. Future studies involving animal models will be needed to further explore the utility of Ag-MIONs, Ag-MIONs@MGK33, Cu-MIONs and Cu-MIONs@MGK33 as anti-TB agents and further validate their bioactivities.