Influence of protein composition on thermodynamics of biomolecular interactions of iron oxide nanoformulations

Iron oxide nanoformulation-based drug delivery system is indeed a fascinating and rapidly developing application of nanotechnology in cancer theranostics. However, limited studies have been performed on quantitative nano-bio interactions and their correlation with therapeutic efficiency. Thus, here we have reported the synthesis and characterization of iron oxide nanoclusters encapsulated into protein (protein-IONCs) along with bare-iron oxide nanoformulation for drug delivery applications. The quantitative insights into the interaction of synthesized nanoformulations with DNA and HSA have been correlated with their therapeutic efficiency to derive quantitative structure–activity relationship (QSAR) for the future designing of efficient drug delivery systems. Results of the experiments suggest that protein-IONCs showed better interaction with biomolecules and enhanced therapeutic efficiency for anti-cancer drugs 5-fluorouracil and doxorubicin hydrochloride and hence act as a better drug delivery system in comparison to bare-iron oxide nanoformulation. Notably, a significant effect of the amino acid composition of protein used for encapsulating IONCs on their binding interactions and therapeutic efficiency was observed. Findings emphasized how slight changes in the number of polar and non-polar amino acids of the protein used for encapsulating IONCs significantly shift the thermodynamic driving forces from enthalpically driven to entropically driven interactions, which are pivotal for designing more effective nanoformulations for biomedical applications. © 2024 Elsevier B.V.