Spectroscopic Insights into Nanodiamond-Doxorubicin Interactions in Drug Delivery Systems for Potential Cancer...

Background/Objectives: Non-covalent nanocarrier-based systems have become a promising platform as they offer a strategy to improve the efficacy-safety profile of doxorubicin (DOX) without altering its chemical structure. Praised for biocompatibility and rich surface chemistry, nanodiamonds (NDs) have launched as nanocarriers of choice for advanced cancer therapy. By investigating DOX-ND physicochemical interactions, this work advances the structural understanding of a non-covalent potential anticancer system, which has not been quantitatively experimentally explored so far. Methods: To our knowledge, this is among the first studies combining ultraviolet-visible (UV-VIS) spectroscopy with spectral deconvolution to reveal the redistribution of different DOX species in the presence of NDs. Centrifugation-assisted analysis enabled differentiation between hypothetical labile and stable ND/DOX fractions. Adsorption kinetics was studied, and dynamic light scattering (DLS) measured particle size and zeta potential. In vitro screening was performed in non-malignant fibroblasts (MRC-5) and malignant melanoma (HS294T), glioblastoma (U251), and breast cancer (MCF-7) cells to evaluate ND/DOX combinations. Results: Centrifugation analysis revealed heterogeneous ND-DOX binding. Kinetic experiments showed fast multi-stage adsorption kinetics, best described by a bi-exponential decay function and the Weber-Morris model. DLS suggested stable systems with a particle size within 10-80 nm, predominantly around 20 nm, and positive zeta potential. Comparative in vitro screening demonstrated differential cellular responses across cell types, highlighting the relevance of ND/DOX interactions. Conclusions: The findings contribute to elucidating ND-DOX interactions relevant for the design and optimization of drug delivery systems, emphasizing the importance of spectroscopic insights for the design of nanodiamond-based drug delivery systems.