From Self-assembly to Smart Delivery: Construction Strategies and Frontier Applications of Prolamin-based Multicomponent Complex Nanocarriers

This review synthesizes recent advances in prolamin-based multicomponent nanocarriers, with a focus on their physicochemical properties, modification strategies, and potential applications in functional foods, biomedicine, and sustainable agriculture. The abundance of hydrophobic amino acid residues in prolamins facilitates spontaneous self-assembly into nanoparticles, making them promising carriers for poorly water-soluble bioactive compounds such as curcumin and resveratrol. However, native prolamin nanoparticles suffer from limitations including poor colloidal stability, tendency to aggregate under processing or physiological conditions (<italic>e.g.</italic>, pH, ionic strength, enzymatic degradation), and limited functional diversity. To address these drawbacks, extensive research has been devoted to modification strategies aimed at enhancing stability, structural integrity, and cargo protection. Polysaccharide modification enables the formation of stable core-shell structures through electrostatic interactions, hydrogen bonding, and steric hindrance. Coatings with pectin, chitosan, or alginate improve stability across a broad range of pH values and ionic strengths, enhance resistance to gastric digestion, and enable sustained release in the intestine, thereby improving bioavailability. Polyphenol modification introduces hydrogen bonding, hydrophobic interactions, and occasionally covalent cross-linking, which modify nanoparticle structure and surface properties. These composites exhibit improved hydrophilicity, colloidal stability, and resistance to oxidative or UV-induced degradation, along with intrinsic antioxidant activity. Lipid modification leverages hydrophobic interactions with oils or fatty acids to form composite nanoparticles or Pickering emulsions. This approach increases the loading capacity for hydrophobic compounds, creates a protective barrier, and enhances oral bioavailability by promoting emulsification and intestinal absorption. Additional strategies include the incorporation of auxiliary proteins (<italic>e.g</italic>., casein, whey protein) to improve stability and emulsifying capacity, as well as the use of inorganic nanomaterials (<italic>e.g.</italic>, SiO₂, AuNPs) to impart mechanical reinforcement, antibacterial properties, and stimuli-responsive functions. Genetic engineering further allows molecular-level tailoring of amino acid sequences to fine-tune hydrophobicity, amphiphilicity, and self-assembly behavior. These engineered nanocarriers exhibit advanced functionalities. They enable sustained and stimuli-responsive release triggered by pH, redox potential, enzymes, temperature, or light, facilitating on-demand delivery that maximizes efficacy while minimizing off-target effects. Targeting can be achieved passively through the enhanced permeability and retention (EPR) effect, or actively <italic>via</italic> conjugation with ligands, antibodies, or peptides that recognize specific receptors. The applications of these systems are broad. In functional foods and nutraceuticals, prolamin-based carriers improve the stability, bioavailability, and controlled release of sensitive bioactive ingredients, supporting personalized nutrition. In biomedicine, they enhance oral drug delivery, enable targeted cancer therapy with reduced systemic toxicity, and serve as scaffolds for tissue engineering. In agriculture, they facilitate the controlled release of pesticides, fertilizers, and growth regulators, helping to reduce environmental contamination and promote sustainable practices; they are also being explored for smart food packaging applications. Despite significant progress, challenges remain in clinical and industrial translation. There is an urgent need for standardized characterization methods, comprehensive <italic>in vivo</italic> safety and efficacy evaluations, and scalable, regulation-compliant manufacturing processes. Future research should adopt rational design principles to develop multi-stimuli-responsive and sustainable systems. The integration of artificial intelligence and data-driven approaches may further accelerate the development of personalized theranostic platforms and co-delivery systems. Continued innovation is expected to solidify the role of prolamin-based nanocarriers in advancing global health and sustainable development.