2571 - Design and Development of Lactoferrin Nanoparticles Encapsulating a Yttrium Curcumin Complex for Macrophage Targeted Redox Modulation with Potential Radiation Applications.

Purpose/Objective(s): Yttrium-based nanomaterials have demonstrated radiation-enhancing potential through modulation of oxidative stress pathways. Curcumin, a metal-chelating polyphenol with established redox activity, can function as a biologically compatible ligand to regulate intracellular reactive oxygen species (ROS). Given the central role of macrophages in radiation response and tumor microenvironment remodeling, we hypothesized that a biologically targeted yttrium–curcumin nanoparticle platform could modulate macrophage intracellular redox signaling without inducing cytotoxicity, thereby providing a mechanistic foundation for immune-mediated radiation enhancement. We therefore designed lactoferrin-based nanoparticles (Lf-NPs) encapsulating a yttrium–curcumin (Y–Cur) complex and evaluated macrophage uptake, cytocompatibility, and ROS modulation.

Materials/Methods: The Y–Cur complex was synthesized via metal chelation of curcumin with yttrium ions and incorporated into lactoferrin nanoparticles using a controlled desolvation method. Nanoparticles were characterized for size distribution, stability, and encapsulation efficiency. In vitro studies were performed using macrophage cell models to evaluate nanoparticle internalization, cell viability, and intracellular ROS levels following treatment with Lf–Y–Cur nanoparticles.

Results: Lf–Y–Cur nanoparticles demonstrated efficient macrophage uptake consistent with lactoferrin receptor–mediated internalization. Macrophage viability was preserved across the tested concentration range, indicating cytocompatibility. Treatment with Lf–Y–Cur nanoparticles resulted in increased intracellular ROS levels significantly compared with controls, demonstrating effective redox modulation without overt cytotoxicity.

Conclusion: We developed a macrophage-targeted yttrium nanoparticle platform capable of modulating intracellular redox signaling while maintaining immune cell viability. These findings extend prior yttrium-based radiation enhancement strategies toward a biologically targeted and translationally accessible system and provide a foundation for future studies investigating immune-mediated radiosensitization and amplification of radiation-induced oxidative stress within the tumor microenvironment.