Rice bran protein-based self-propelled nanomotors for targeted delivery of dihydroquercetin: A food-grade nano-system for anti-atherosclerosis.

Dihydroquercetin (DHQ), a natural flavonoid with promising anti-atherosclerotic activity, faces major clinical translation challenges due to its poor aqueous solubility and low oral bioavailability. Self-propelling nanomotors, capable of converting chemical energy from pathological microenvironments into autonomous motion, offer a novel strategy to overcome biological barriers and achieve targeted delivery. This study developed an edible, self-propelling nanomotor (NM) based on sustainable rice bran protein (RBP) for the targeted oral delivery of DHQ. To address the multiple delivery challenges of dihydroquercetin, the system was rationally engineered with integrated functions via a multi-stage modification protocol. Initial fabrication of RBP-DHQ nanoparticles provided a biocompatible core for drug encapsulation, after which sequential functionalization with L-arginine and D-mannose was implemented to simultaneously achieve ROS-triggered self-propulsion and macrophage-targeted accumulation. A Spirulina-derived microalgal coating was further incorporated as the outermost layer, with the specific purpose of shielding the payload from degradation within the gastrointestinal tract.The optimized NM exhibited a small size (498.6 ± 7.5 nm), high encapsulation efficiency (92.8 ± 0.8 %), and concentration-dependent propulsion (velocity up to 28.31 ± 2.22 μm/s in 10 mM H₂O₂). In vitro studies showed that the NM achieved 2.3-fold higher cellular uptake in macrophages compared to non-targeted nanoparticles and enhanced the oral bioavailability of DHQ by 16.6-fold. In an atherosclerotic macrophage model, the NM effectively restored cell viability, scavenged intracellular ROS, and markedly reduced lipid accumulation.This integrated platform, which combines an edible matrix with endogenous stimulus-driven propulsion and active targeting in a food-grade system, establishes a novel strategy for the precise nutritional management of atherosclerosis and other inflammatory diseases.