Metal nanofungicides as emerging tools for crop disease control: an opinion article

Cecilia Hernández-RamírezJesusita Rosas-DiazMario J. Romellón-CerinoAntonio Priego-ClementeHeriberto Cruz-Martínez^*

• Tecnologico Nacional de Mexico, Mexico City, Mexico

Phytopathogenic fungi represent a significant challenge in agriculture due to their high incidence and severe losses in various crops. These pathogens are responsible for numerous foliar, root, and vascular diseases, including rusts, downy mildews, anthracnose, and wilts, which affect plant physiology and compromise the yield and quality of harvested products (1,2). Fungal diseases are estimated to cause losses of 10-15% in the world's major crops (3). In this regard, various strategies have been studied and implemented to control these pathogens and reduce their economic impact.Currently, these microorganisms are mainly controlled with synthetic agrochemicals, which are generally inexpensive and readily available. However, their indiscriminate use has led to various challenges, including environmental contamination, human poisoning, and alteration in soil properties (4,5). Also, fungi have developed greater resistance to chemical agents, making their control more difficult (6,7). Therefore, several environmentally friendly alternatives have been investigated, highlighting the use of nanomaterials to control these microorganisms (8,9). Different nanomaterials have been investigated recently (e.g., nanocomposites, nanocarbons, nanogels, nanocapsules, nanoemulsions) and have exhibited good antifungal activity against phytopathogenic fungi (10,11). Among these studied nanomaterials, metal nanoparticles have been the most widely investigated, as they have demonstrated good antifungal activity against various phytopathogenic fungi (12, 13).Currently, numerous types of metal nanoparticles have been investigated as nanofungicides for controlling different crop diseases. However, despite the promising results reported in multiple studies, several aspects still require further analysis and discussion. Therefore, this opinion article presents the current state of the application of metal nanoparticles as fungicides and discusses the main challenges associated with their use in agricultural systems. Metal nanoparticles are emerging as an innovative alternative for controlling phytopathogen fungi in agriculture. The good antifungal activity of these nanoparticles can be attributed to their unique characteristics, including small dimensions (1-100 nm), which therefore results in a higher surface-tovolume ratio. Also, these nanoparticles exhibit quantum effects that can enhance their properties compared with those of the bulk material (14,15). To date, numerous review articles have examined the use of metal nanoparticles to control phytopathogenic fungi in crops (12,13,(16)(17)(18). Monometal, bimetal, and trimetal nanoparticles have been produced, with monometal nanoparticles being the most studied (Figure 1a). Among the monometal nanoparticles, Ag nanoparticles are the most widely studied, followed by Cu nanoparticles, and the other monometal nanoparticles have been studied to a lesser extent (12). As in the case of pure metallic nanoparticles, various types of monometal, bimetal, and trimetal oxide nanoparticles have been produced and evaluated against different phytopathogenic fungi, with monometal oxide nanoparticles being the most explored (Figure 1b). Within these, ZnO nanoparticles are the most investigated, followed by CuO nanoparticles (17). Metal and metal oxide nanoparticles have been produced using various synthesis routes, highlighting the chemical and biological methods. These routes have mainly produced spherical nanoparticles with polydisperse sizes (12,13,(16)(17)(18). Fortunately, some produced nanoparticles exhibited controlled shape, such as truncated octahedrons, hexagonal and cubic structures, lamellar platelets, and nanorods (19)(20)(21)(22)(23)(24). Also, a large number of commercially acquired nanoparticles have been evaluated for controlling phytopathogenic fungi (12,17). The antifungal activity of these nanoparticles against phytopathogenic fungi has been assessed under both in vitro and in vivo conditions, with in vitro studies being the most widely reported (12,17).Under in vitro conditions, antifungal activities greater than 90% have been achieved at concentrations of 1000 ppm or higher for most metal nanoparticles (12,17). Also, under in vivo conditions, metal and metal oxide nanoparticles have also shown considerable potential for controlling fungal diseases in different crops (25)(26)(27)(28). Significant progress has been made in the application of metal and metal oxide nanoparticles for controlling phytopathogenic fungi, with studies indicating their potential as effective alternatives to conventional chemical fungicides in crop protection (12,13,(16)(17)(18). However, there are several points that need to be analyzed and discussed:1. The antifungal activity of metal nanoparticles is influenced by several characteristics, including size, shape, surface chemistry, crystalline structure, stability, dispersion, and specific surface area (12,17). However, to date, the effects of nanoparticle size and shape on antifungal activity have been only partially addressed (12,13,(16)(17)(18). Therefore, it is essential to study in detail the influence of the size and shape of metal nanoparticles on their antifungal activity, as these physicochemical properties are known to play a critical role in their effectiveness (12,17). Furthermore, other nanoparticle characteristics such as surface chemistry, crystalline structure, stability, dispersion, and specific surface area must be evaluated to fully understand the role that each one plays in antifungal activity. Evaluation of antifungal activities: Nanoparticle evaluations against phytopathogenic fungi have been conducted under both in vitro and in vivo conditions, with in vitro evaluations being the most widely used (12,17). The antifungal activities observed under in vitro assays are promising (12,13,(16)(17)(18). However, it is crucial to conduct further in vivo studies, as these experiments provide a more accurate assessment of the effectiveness of metal nanoparticles in controlling phytopathogenic fungi because several factors can influence nanoparticle performance, including the type of fungus, the crop species and developmental stage, environmental conditions (e.g., humidity, temperature, and pH), and the application method and concentration of nanoparticles. Synthesis methods: Metal nanoparticles have been produced mainly using chemical and biological routes (12,13,18). The biological route stands out as a greener alternative, as it employs plant-or microorganism-derived extracts as reducing agents, making it considerably more environmentally friendly (12,17,18). On the other hand, chemical methods can sometimes produce waste that harms the environment. Despite the clear benefits of the biological approach, it does have its challenges. Standardizing this method can be tough, and scaling up production to produce several grams of metal nanoparticles can be even more complicated. In contrast, chemical methods can be more easily scaled up and provide better control over the size and shape of the metal nanoparticles. Therefore, it is crucial to choose a synthesis method that produces nanoparticles with homogeneous sizes and shapes and can also be easily scaled up for largerscale production. Bimetal and trimetal nanoparticle synthesis: It is essential to synthesize and evaluate additional bimetal or trimetal nanoparticles for controlling phytopathogenic fungi. Bimetal and trimetal nanoparticles are important because they can exhibit superior properties compared to monometal nanoparticles (29,30). By combining two or three metals, the chemical reactivity, stability, and selectivity can be improved. These combinations allow for synergistic effects, in which the metals work together to generate novel properties that do not exist individually, as demonstrated in other applications (29, 30). Potential environmental impact: Like other synthetic agrochemicals, metal nanoparticles may pose environmental risks if they leak into soil or water, potentially affecting non-target microorganisms (17,31). Their persistence in the environment could alter soil microbial communities, disrupt nutrient cycles, and negatively influence beneficial organisms. In aquatic systems, the accumulation of metal nanoparticles may lead to toxicity in algae and invertebrates. Therefore, their potential environmental impacts must be carefully studied before they are widely used to control phytopathogenic fungi, including assessments of their long-term behavior, bioaccumulation potential, and ecological safety. Resistance risk: As with most commercial agrochemicals, the repeated and prolonged use of metal nanoparticles as nanofungicides can exert intense selective pressure on fungal populations, thereby favoring the emergence and spread of resistant strains (32). Such resistance could significantly reduce the long-term effectiveness of metal nanoparticles and compromise their potential advantages over conventional fungicides. Consequently, it is essential to develop and implement appropriate resistance management strategies, such as optimizing application doses and frequencies, rotating or combining nanofungicides with other control agents, and integrating their use within broader disease management programs, to minimize the likelihood of resistance development in target microorganisms and ensure sustainable agricultural practices.In conclusion, significant progress has been made in the use of metal nanoparticles as fungicides for various crops. However, several points still need to be addressed in detail before their widespread implementation.