Oxidized and amino-functionalized nanodiamonds as shuttle for delivery of plant secondary metabolites: Interplay between chemical affinity and bioactivity

Abstract This study is focused on the surface engineering of detonation nanodiamonds (DND) for the delivering of therapeutic agents, and on the developing of strategies for the DND conjugation with biologically active substances. Oxidized and differently amino-functionalized DND have been investigated to identify their chemical and structural features. A series of complexes have been produced by reacting the activated DND particles with four antioxidant molecules abundant in grapes and wine: resveratrol (R), rutin hydrate (U), epicatechin (E) and chlorogenic acid (C). Drug up-take is found strictly dependent on the affinity between molecules and selectively modified DND surfaces. All adducts, prepared avoiding potentially toxic solvents, reached a concentration suitable for therapeutic applications. MTT assay, performed on SH-SY5Y neuroblastoma cell line, evidenced that the conjugation with DND amplifies the bioactivity of the metabolites with respect to the relative pure molecules. However, depending on the DND surface chemistry, the various metabolites are found to exert markedly different effects on tumor cell viability, producing increase or decrease of proliferation. These findings indicate that a tailoring of the DND surface chemistry, specific for each molecule, is required not only to improve binding/delivering of active substances to biological targets, but also to achieve the desired therapeutic results.