*3.2. Antifungal Nanomaterials for Management of Mycotoxins in Animal Feeds*

The morbidity and mortality caused due to global incidences of mycotoxicosis in animal and poultry industry have serious economic repercussions affecting the productivity [1,3,5,93]. Recently, it was reported that ZnO NPs and Fe2O<sup>3</sup> NPs have antifungal activity against ochratoxigenic *Aspergillus* and hence prevent mycotoxin synthesis [57,65]. The supplementation of Zn NPs in aflatoxicated feed of rats and rabbits resulted in the removal of the carcinogenicity of aflatoxins on the kidney and liver [72,94]. The ZnNPs and AgNPs can inhibit the growth of *Fusarium poae* and prevent formation of trichothecenes mycotoxin [16]. The Ag NPs can eliminate aflatoxins in chickens feed [95,96]. Biosynthesized spherical SeNPs produced by *Saccharomyces cerevisiae* and originated from selenous acid and sodium sulfite were able to inhibit pathogenic saprophytes, yeasts, and dermatophytes [97]. Fadl et al. [98] have reported that CuNPs inhibit ochratoxigenic molds and prevent ochratoxin production in a fish feed.

Apart from the metal/metal oxide nanoparticles, carbon nanomaterials, particularly carbon nanodiamonds, can ameliorate the adverse effects of mycotoxins by the process of immobilization of the mycotoxins [99]. While, another report by Hassan et al. [3] detected the activity of CNTs in suppression the toxicity of *A. flavus* at a concentration of 125 µg/mL. Therefore, the primary modus operandi for the anti-mycotoxigenic effects of both nanomaterials and nanocomposites such as iron NPs [100] and MgO-SiO<sup>2</sup> nanocomposite [101] is through adsorption of the mycotoxins.

Nanohybrids such as polyene-functionalized magnetic NPs possess enhanced antifungal activity against opportunistic oral fungal pathogens such as *Candida* sp. [102]. A miconazole nanocarrier (MCZ) based on iron oxide nanoparticles (IONPs) functionalized with CS was prepared, characterized and screened for antifungal activity against *Candida albicans* and *Candida glabrata* biofilms. A nanocarrier with less than 50 nm dimeter presenting MIC values lower than those observed for high diameter and showed synergism against *C. albicans* [103]. Similarly, nanoformulations of known antifungal agents can improve the action spectrum of these agents and enhance the antibiofilm potential. The antimicrobial and antibiofilm effects of a colloidal nanocarrier for chlorhexidine (CHX) on yeast and bacteria such as *Candida glabrata* and *Enterococcus faecalis* were evaluated. The CHX nanocarrier has an excellent ability for the management of oral diseases linked to *C. glabrata* and *E. faecalis* [104].

The nanocomposites derived from metal oxide and carbon nanomaterials have also been evaluated for anti-mycotoxin properties. A magnetic carbon nanocomposite derived from bagasse was observed to degrade AFB1 [105], while graphene oxide nanocomposites caused a reduction in the occurrence of three prominent *Fusarium* toxins i.e., ZEA, FB, and deoxynivalenol [106] and modified halloysite nanotubes [96,107]. Also, detoxification of AFB1 by a magnetic graphene oxide nanocomposite has been reported by Ji and Xie [108]. González-Jartín et al. [109] observed that nanocomposites of carbon, bentonite, and aluminum oxide eliminated up to 87% of the mycotoxins with an adsorption efficiency of 450 µg/g. Chitosan-stabilized selenium nanoparticles have a significant ability to improve the toxic effects of aflatoxicosis in rats [35,110]. Further, the SeNPs exhibited important inhibitory effects on *A. parasiticus, A. ochraceus,* and *Aspergillus nidulans* growth at concentrations varying from 0.1–0.5 mg/L and ameliorate the dysfunction and hepatic apoptosis induced by AFB1 [30]. Chitosan-coated Fe3O<sup>4</sup> particles have been reported to be substantially useful for patulin decontamination with no toxic response or histopathology in treated mice [106,111]. Recently, Hassan et al. have also assessed the efficiency of the copper-CS nanocomposites for the removal of the aflatoxins and ochratoxins in poultry (personal communication).

Conjugating metal oxide nanoparticles with other antimicrobial components such as essential oils, curcumin or ozone can improve the antimycotoxigenic activities. Also, the antimicrobial, anti-aflatoxins, and anti-shigella toxins potentials of nanoemulsion of cinnamon oil and ZnO NPs towards to fungal causes of dysentery in buffaloes were detected [16]. Hassan et al. [72] observed that conjugating ZnO-NPs along with probiotic and curcumin improved the inhibitory activities on mycotoxin producing *Fusarium* sp. besides significantly decreasing their ability for mycotoxin production. The combined application of ZnO NPs, probiotic and curcumin (ZnO NPs (100 µg/mL) + probiotic (0.5%) or curcumin (0.5%)) resulted in complete detoxification of *Fusarium* mycotoxins [72]. Hassan et al. [16] reported alteration in the gene expression profile of the ZnO and essential oil treated *E. coli* and *A. flavus* through RT-PCR studies that helped to elucidate the efficacy of the treatments. When the treatment doses of ZnO NPs, cinnamon oil, and olive oil increased, the AflR and Stx toxin genes expression efficacy, the molecular weight of DNA, and cycle threshold were decreased. The synergistic activity used lower doses of combined form than each alone. Hamza et al. [112] used hybrid β-glucan mannan lipid particles (GMLPs)-humic acid iron nanoparticles (HA-FeNPs) as an AFB1 binder provides a high binding capacity and a safe enhanced mycotoxin binding material.
