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, monoand 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 NiMIONs@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 mu g/mL respectively. Functionalized Cu-MIONs@MGK33 and AgMIONs@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 mu g/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, CuMIONs and Cu-MIONs@MGK33 as anti-TB agents and further validate their bioactivities.