Soybean (Glycine max) is a crop of global significance and has low reliance on N fertilizers due to its biological nitrogen fixation (BNF) capacity, which harvests ambient N₂ as a critical ecosystem service. BNF can be severely compromised by abiotic stresses. Enhancing BNF is increasingly important not only to alleviate global food insecurity but also to reduce the environmental impact of agriculture by decreasing chemical fertilizer inputs. However, this has proven challenging using current genetic modification or bacterial nodulation methods. Here, we demonstrate that a single application of a low dose (10 mg/kg) of molybdenum disulfide nanoparticles (MoS₂ NPs) can enhance soybean BNF and grain yield by 30%, compared with conventional molybdate fertilizer. Unlike molybdate, MoS₂ NPs can more sustainably release Mo, which then is effectively incorporated as a cofactor for the synthesis of nitrogenase and molybdenum-based enzymes that subsequently enhance BNF. Sulfur is also released sustainably and incorporated into biomolecule synthesis, particularly in thiol-containing antioxidants. The superior antioxidant enzyme activity of MoS₂ NPs, together with the thiol compounds, protect the nodules from reactive oxygen species (ROS) damage, delay nodule aging, and maintain the BNF function for a longer term. The multifunctional nature of MoS₂ NPs makes them a highly effective strategy to enhance plant tolerance to abiotic stresses. Given that the physicochemical properties of nanomaterials can be readily modulated, material performance (e.g., ROS capturing capacity) can be further enhanced by several synthesis strategies. This study thus demonstrates that nanotechnology can be an efficient and sustainable approach to enhancing BNF and crop yield under abiotic stress and combating global food insecurity.

Significance: This study analyzed the dynamic protein corona on the surface of nanoparticles as they traversed from blood to cell lysosomes and escaped from lysosomes to cytoplasm in the target cells. We found with proteomic analysis an abundance of chaperone and glycolysis coronal proteins (i.e., heat shock cognate protein 70, heat shock protein 90, and pyruvate kinase M2 [PKM2]) after escape of the nanoparticles from lysosomes to the cytosol. Alterations of the coronal proteins (e.g., PKM2 and chaperone binding) induced proteostasis collapse, which subsequently led to elevated chaperone-mediated autophagy (CMA) activity in cells. As PKM2 is a key molecule in cell metabolism, we also revealed that PKM2 depletion was causative to CMA-induced cell metabolism disruption from glycolysis to lipid metabolism.