Effects of diamond nanoparticle surface composition and the sp(3)/sp(2) carbon ratio on tumor proangiogenic potential in vitro.

The high proangiogenic potential of tumors is often associated with poor prognosis due to increased invasiveness and malignancy. Diamond nanoparticles (NDs) are considered a promising anti-tumor agent with anti-angiogenic properties; however, their activity is strictly connected with their physicochemical parameters and surface chemical composition. One of the main factors characterizing detonation NDs is the sp(2) surface carbon content, which can determine the character of nanoparticle-cell interaction. The primary objective of this study was to investigate the influence of different types of NDs on the proangiogenic potential of tumor cells distinguished by phenotype and invasiveness. NDs with a high sp(3)/sp(2) carbon ratio decreased the levels of crucial proangiogenic proteins secreted by T98G and HepG2 cells (IL-6, IL-8, ANG, TIMPs, and ANGPTs). Moreover, a lower sp(2) carbon content on the surface of NDs reduced oxidative stress in both mesenchymal T98G and epithelial HepG2 tumor cells and affected the NF-κB activation state in a cell-specific manner. Modified NDs, by affecting the tumor cell secretome composition, indirectly inhibited endothelial cell migration and tube formation, demonstrating high cell type specificity. Taken together, the results presented here indicate the significance of the surface parameters of NDs in the indirect regulation of cellular signaling and the microenvironment.