We employed a combined experimental and analytical approach to investigate the influence of nanoparticle geometry on the loading efficiency of doxorubicin (DOX) onto \(\hbox {CeO}_2\) nanoparticles. Experimentally, three distinct \(\hbox {CeO}_2\) shapes, spherical, sheet, and cylindrical, were synthesized, characterized, and their respective DOX loading efficiencies were measured. Concurrently, analytical mathematical models were developed to calculate the van der Waals (vdW) interaction energy between a spherical DOX molecule and each nanoparticle geometry, considering both theoretical loading and surface adsorption scenarios. The model successfully predicted the relative thermodynamic stability by yielding high and similar binding energies for the spherical and sheet geometries, which aligned well with their high experimental loading efficiencies. However, a significant quantitative discrepancy arose with the cylindrical shape, where the predicted binding energy did not correspond to the high experimental loading efficiency. This divergence powerfully demonstrates that a simple vacuum-based vdW model is fundamentally insufficient to fully capture the complexity of the drug-nanoparticle interaction. Despite this limitation, the synergy between experimental validation and theoretical modeling provides a critical framework for understanding the geometric dependence of drug-nanoparticle interactions and guides future model refinement toward incorporating the complexity of the nano-bio interface.
