Engineering zein/polydeoxyribonucleotide nanocomposite particles as stable and multifunctional carriers

Reactive oxygen species (ROS)-induced oxidative stress impedes efficient wound healing, while the therapeutic application of hydrophobic bioactive compounds is severely limited by poor water solubility, stability, and bioavailability. Herein, naturally derived zein/polydeoxyribonucleotide (Zein/PDRN) nanocomposite particles were fabricated through an antisolvent method to stabilize curcumin and enhance its biological activity. PDRN regulated zein self-assembly in a concentration-dependent manner, producing homogeneous nanocomposite particles with enhanced colloidal stability under diverse environmental conditions. Spectroscopic analyses and molecular docking revealed that electrostatic interactions, hydrogen bonding, hydrophobic interactions, and van der Waals interactions cooperatively contributed to particle formation and stabilization. The optimized formulation achieved a curcumin encapsulation efficiency of 90.16% with a loading capacity of 6.01%, while considerably improving its resistance to ultraviolet (UV) irradiation and thermal treatment and enabling sustained curcumin release. More importantly, PDRN imparted intrinsic biological function to the nanocomposite particles, and its combination with curcumin produced enhanced antioxidant and cytoprotective effects, including enhanced free radical scavenging, inhibition of oxidative erythrocyte hemolysis, favorable cytocompatibility, and enhanced fibroblast migration in vitro. This work demonstrates that biopolymers can function not only as structural stabilizers but also as bioactive components, providing a simple strategy for engineering multifunctional carriers for biomedical and cosmetic applications.