ИСТИНА

Due to notable biocompatibility and possibilities of surface conjugation, nanodiamonds (ND) have recently attracted high attention in regard to their potential applications in biology and medicine, especially, for bioimaging and drug delivery. Remarkable fluorescence and Raman spectroscopic properties make ND an efficient biomarker for tracking the interactions of specific molecules with biological systems. In this paper, we present our results in studying the effects of ND on different live cells in the context of drug delivery and, also, in bio-labeling using ND’s fluorescence and Raman properties. Using ND for both drug delivery and diagnostics presumes their administration into the organism, in particular, by injecting them intravenously into the blood circulation. Using different optical techniques (optical and fluorescence microscopy, Raman microspectroscopy, diffractometry, diffuse light scattering, optical trapping, etc.) we studied the interaction of sole ND of different sizes and ND in complex with biologically active molecules (proteins, drugs) with blood cells and blood plasma proteins with special focus on red blood cells (RBC) in vitro and in vivo. We showed that ND do interact with RBC membrane in a concentration dependent manner. This interaction can influence the membrane structure and affect the RBC mechanical and microrheological properties, deformability and aggregation, which in turn can affect the blood rheology and microcirculation. We compared the ND effects on the processes of oxygenation and deoxygenation of whole RBC and of hemoglobin in solution. It was shown that preliminary modification of ND surface with blood plasma protein albumin significantly increases the biocompatibility of ND at its interaction with blood, including its effects on RBC functioning and on blood plasma composition and properties, particularly, decreasing the uncontrollable adsorption of plasma components. However our Raman microspectroscopy experiments revealed possible effects on the secondary structure of albumin of its adsorption on ND surface. This may potentially lead to the alteration of albumin functional activity. Similar effects on fibrinogen and globulins, strongly deterimining the aggregation properties of RBC are currently under investigation. Different methods were developed to functionalize the ND surface with various functional groups, which allow further conjugation with biomolecules via either physical (electrostatic) or chemical (covalent bonding) interactions. The developed ND-biomolecule conjugate serves as a nanobio-probe to label bio-interaction. We successfully used ND to label the interaction of growth hormone (GH) and growth hormone receptor (GHR) on human lung cancer cell (A549) membrane surface. To conclude, the performed experiments demonstrate the ND’s high potential in biomedical applications based on the properties of uptake ability, detectability and little cytotoxicity in human cells.