Computational Analysis of Doxorubicin-Encapsulated Zein Nanoparticles: A Synergistic Strategy for Targeted Cancer Drug Delivery

Doxorubicin, a widely used chemotherapeutic drug of the anthracycline family, remains among the most efficient agents in cancer treatment. However, its clinical applications are often restricted by systemic toxicity, drug resistance, and poor targeting capacity, highlighting the necessity of advanced delivery systems. In this study, we introduce a novel approach based on doxorubicin-loaded zein nanoparticles (Doxorubicin-LNPs) as a carrier system for targeted drug delivery. Zein, a hydrophobic plant-derived protein, was selected as a carrier due to its biocompatibility, biodegradability, and capacity to interact with hydrophobic and amphiphilic molecules. Its integration with doxorubicin, an amphiphilic drug, demonstrates the adaptability of zein in encapsulating diverse therapeutic agents. To reinforce the stability of the encapsulation matrix, the cross-linker EDC was incorporated, ensuring enhanced structural integrity and sustained release. Extensive characterization studies confirmed favorable physicochemical properties, high encapsulation efficiency, and controlled release behavior of the formulated nanoparticles. Furthermore, molecular docking was conducted to explore the interactions among zein, doxorubicin, and EDC, providing molecular-level evidence of the stability and binding mechanisms within the system. The overall findings confirm that Doxorubicin-LNPs not only achieve efficient drug loading and prolonged release but also exhibit anticancer activity, making them a candidate for improving therapeutic outcomes. This innovative formulation paves the way for the development of advanced zein-based nanocarriers in targeted cancer therapy and broader biomedical applications.