Nanodiamonds modified with functional groups are obtained for targeted drug delivery. A set of methods for identifying nanodiamonds in biological material is determined and their localization in human macrophages and mouse lung cells is identified. It is shown that seven days after introduction into the mouse lungs, nanodiamonds are internalized by endotheliocytes and interstitial macrophages. Both in the human macrophage culture and in the lung cells, nanodiamonds are localized in phagosomes/phagolysosomes. The nanodiamonds do not cause pathological changes in human macrophages and mouse lung cells. The results obtained lead us to consider nanodiamonds as a promising carrier platform for drug delivery, first and foremost to macrophages of the interstitium of the respiratory portion of the lung, which is relevant in such a disease as tuberculosis.

Today nanomaterials, including carbon ones, considered to be promising radionuclide carriers for nuclear medicine. We previously determined that nanodiamonds (NDs) have the best sorption properties in comparison to other carbon nanomaterials for the range of medical radionuclides including 90Y. At the same time, it was shown that the surface composition of NDs does not influence sorption and desorption for this isotope. In this work the influence of aggregate sizes of NDs and ζ-potential of their surface in water solutions on their sorption and desorption is studied, using 90Y as an example. It was determined that with the increase in aggregate sizes and decrease in ζ-potential the sorption decreases, which lets specify the mechanism of binding of 90Y to NDs. It was shown that creation of suspension with determined sizes of particles is an important task for the future use of NDs as medical radionuclide carriers.

Nanodiamonds (NDs) were investigated as potential carriers of 99mTc, which is widely used for the diagnosis of diseases in nuclear medicine. The sorption of 99Tc(VII), 99mTc(VII), and 99mTc(IV) by commercial NDs and their reduced, aminated, and oxidized forms was studied. The physicochemical parameters of the Langmuir and Freundlich isotherms for the sorption of 99Tc(VII) by the used ND samples were determined. The Sn(II): Tc(VII) ratio for the quantitative reduction of Tc to the oxidation state IV was optimized. It was shown that the initial (commercial) and oxidized NDs are promising carriers of 99mTc(IV) for nuclear medicine.

In this study, the possibility of application of carbon nanomaterials (CNMs) as carriers of various isotopes for nuclear medicine is investigated. The sorption of Tc-99m, Bi-207 (as analog for Bi-213), Y-90, and Ra-226 (as analog for Ra-223) in aqueous solutions with pH 6 and 0.01 M phosphate-buffered saline with pH 7 was studied on the following CNMs samples: detonation nanodiamonds (NDs), reduced graphite oxide (rGiO), and multi-walled nanotubes (MWCNTs). Commercial, hydrogenated, and aminated ND and hydrogenated MWCNTs adsorb Tc (VII) by 40-70%; however, in physiological saline, it is readily desorbed within 0.5 h. The sorption of Tc(IV) on commercial and carboxylated ND, as well as rGiO, was 60-90%. In this case, desorption in the biological media did not exceed 5% for each sample in 5 h. The sorption of Bi(III) on all the samples studied was from 80% to 100%, and the Bi(III)@ND conjugate was the most stable, as its desorption in the model biological medium was 4% for 5 h. It was shown that the sorption and desorption for Y(III) differs significantly depending on the CNM sample used, thereby allowing for the selection of the conditions for the use of Y(III)@CNMs conjugate for specific medical tasks. It was found that Ra(II) sorption occurs only on the rGiO sample and reaches 60%; however, depending on the medium, desorption was from 35% to 70% in 30 min, thereby complicating the use of the Ra(II)@rGiO conjugate. The data regarding sorption behavior and stability in biological media of the studied isotopes on CNMs allow us to not only choose the conditions for their effective use in nuclear medicine, but also evaluate the sorption behavior of other nuclear medicine isotopes.

A method has been developed for isolation of 228 Ac from aged samples of natural 232 Th. Macroscopic amounts of the thorium bulk (20 g) were separated by its extraction by a solution of di(2-ethylhexyl)phosphoric acid in toluene from 4 M HNO 3 solutions, with microamounts of 228 Ra and 228 Ac remaining in the aqueous phase. 228 Ac was selectively extracted from the resulting solution by the method of extraction chromatography on a column with RE resin sorbent, and 228 Ra quantitatively remained in the 4 M HNO 3 eluate. 228 Ac was washed out of the column with 0.05 M HNO 3 , it could be used as a radioisotope for research purposes. After the accumulation of the daughter 228 Ac the solution of 228 Ra in 4 M HNO 3 was repeatedly passed through an identical column. The resulting 228 Ac was used in the study to examine its sorption on commercial and modified carbon nanomaterials (CNMs) instead of the difficultly accessible 225 Ac. It is shown that the application of CNMs as carriers of actinium isotopes for nuclear medicine purposes is promising.

Information on the use of detonation nanodiamonds (DNDs) in biomedical applications is reviewed. Literature data and our own results on the preparation of DND conjugates with biologically active compounds and the in vivo distribution of nanodiamonds are presented. The main development directions for designing DND systems to deliver biologically active compounds and drugs are identified. DNDs are attractive for biomedical applications because of their property set that includes biocompatibility, the ability to functionalize the particle surface, strong and specific adsorption/conjugation of drugs and biomolecules, large specific surface area, and stable fluorescence.

There were illustrated the main questions of development of new generation drug delivery systems as hybrid nanomaterials as follows: selection of nanocarrier, its standardization and the methods of immobilization of biologically active and medicinal substances. The basic organs of distribution and accumulation of advanced carbon nanocarrier - detonation nanodiamond were identified. It was shown that antihypoxic effect of the nanodiamond-glycine conjugate increased in comparison with a native Glycine and Mexidolum® as reference drugs.

223Ra and 211Pb/211Bi radionuclides with radiochemical purity were obtained from 227Ac/223Ra generator on DGA resin. Covalent grafting of organic complexons (ethylenediaminetetraacetic acid—EDTA and derivatives of amino acids—L1 and L2 to aminated nanodiamonds (ND) was performed by carbodiimide method. Adsorption behavior of Ra and Pb in plasma volume expander on modified nanodiamonds was studied in detail. Effective adsorption have been found for 211Pb in physiologically acceptable conditions. Sorption behavior of generator radionuclides 223Ra and 211Pb on the surface of ND-L1 and ND-L2 in aqueous solution (pH = 6.3) was studied. It was shown that the labeling yield of 211Pb from the solution was about 94%. The sorption of 223Ra under the same conditions was weak. The sorption/desorption kinetics of 211Pb on the surface of ND-EDTA in the plasma volume expander was studied. The desorption rate of 211Pb did not exceed 2.5% within 60 min (pH 7.2–7.4).

In this review, the problems of the development of radiopharmaceuticals (RPs) based on alphaemitting radionuclides are discussed. The prospects of application of the radionuclides 227Th, 225Ac, 223Ra, 213Bi, 212Pb/212Bi, 212Bi, 211At, and 149Tb are estimated in the aspect of their physicochemical properties, such as half-life, properties of daughter radionuclides, and complexing ability. The methods used for the production of radionuclides and their industrial availability are considered. Some examples of radionuclide complexes with ligands and nanoparticles for targeted delivery are presented. The results of medical trials for RPs based on alpha emitters are given.

For the first time, an effect of detonation nanodiamonds (NDs) with different surface compositions on the main functional characteristics of isolated rat liver mitochondria was studied. The response of membrane potential, calcium retention capacity, and redox state of pyridine nucleotides have been monitored upon the administration of NDs functionalized with carboxyl, hydroxyl, amine, hydrogen, and chlorine surface groups. Hydrogenated and chlorinated NDs caused reduction of the membrane potential and calcium retention capacity of mitochondria. An aminated ND caused an even greater decrease in calcium retention capacity (at a concentration of 0.75 mg/ml), reducing it to 65% of the control. The use of cyclosporine A prevented a decrease in membrane potential and calcium retention capacity indicating the induction of non-specific mitochondrial membrane pores during the NDs incubation with mitochondria. Hydrogenated and chlorinated NDs had no significant effect on the redox state of mitochondrial pyridine nucleotides. Other NDs studied had no effects on functional characteristics of mitochondria, even at high concentrations (up to 1.5 mg/ml). High activity of chlorinated and hydrogenated NDs may be due to the greater hydrophobicity of their surface and its interaction with mitochondrial pores components. Thus, isolated rat liver mitochondria can be used as a biomodel for initial testing of ND samples to assess the possibility of their use in drug delivery systems.

The effect of the chemical nature of the surface of detonation nanodiamond on the adsorption of an antibiotic is revealed with the help of tritium-labeled amikacin. It is found that nanodiamonds with a carboxylated surface (Ssp = 283 ± 5 m2/g) chemisorbed twice as much amikacin as nanodiamonds with a hydrogenated surface (Ssp = 289 ± 5 m2/g): 48 and 22 mg/g, respectively. Maintaining nanodiamonds with immobilized amikacin in the form of hydrosol for 1 month results in a release of up to 9.6 and 6.4 mg/g of the antibiotic, respectively. The results demonstrate the possibility of creating an amikacin delivery system based on nanodiamonds.

Two novel conjugates of detonation nanodiamonds (dNDs) with the proteolytic enzymes chymotrypsin and papain were synthesized. The synthesis was performed via functionalization of the dNDs' surface with acidic/alkali treatment followed by carbodiimide-mediated protein binding. Covalent binding of the enzymes was confirmed by Fourier transform infrared spectrographic analysis and high-performance liquid chromatography (HPLC) amino acid analysis. HPLC also proved the preservation of the enzymes' composition during synthesis. The same assay was used to determine the binding ratios. The ratios were 12% (mass to mass) for chymotrypsin and 7.4% for papain. The enzymatic activity of the conjugates was measured using chromogenic substrates and appeared to be approximately 40% of that of the native enzymes. The optimum pH values and stability under various conditions were determined. The sizes of resulting particles were measured using dynamic light scattering and direct electron microscopic observation. The enzyme conjugates were shown to be prone to aggregation, resulting in micrometer-sized particles. The ζ-potentials were measured and found to be positive for the conjugates. The conjugated enzymes were tested for biological activity using an in vitro model of cultured transformed human epithelial cells (HeLa cell line). It was shown that dND-conjugated enzymes effectively bind to the surface of the cells and that enzymes attack exposed proteins on the plasma membrane, including cell adhesion molecules. Incubation with conjugated enzymes results in morphological changes of the cells but does not affect cell viability, as judged by monitoring the cell division index and conducting ultrastructural studies. dNDs are internalized by the cells via endocytosis, being enclosed in forming coated vesicles by chance, and they accumulate in single membrane-bound vacuoles, presumably late endosomes/phagosomes, along with multimembranous onionlike structures. The authors propose a model of a stepwise conjugate binding to the cell membrane and gradual release of the enzymes.

Detonation nanodiamonds (NDs) with chlorinated (ND-Cl) and carboxylated (ND-COOH) surfaces were obtained. The broad-spectrum antibiotic Amikacin (Amik) was covalently grafted to the chlorinated surface (ND-Amik) and immobilized by adsorption to carboxylated surface (Amik/ND-COOH). Biological testing in vitro showed the presence of antibacterial activity of the obtained samples against Staphylococcus aureus FDA P209 and Escherichia coli ATCC 25922, close to activity of free amikacin. It was revealed that to maintain antibacterial activity of the samples after their preliminary treatment, important factors such as the use of antioxidants (hydrosulfite and sodium citrate) and lyophilization were necessary.

Samples of detonation nanodiamonds modified during the synthesis by adding doping elements in various ways have been studied by spectroscopic methods (electron paramagnetic resonance, Raman scattering, and X-ray diffraction). For the first time, the presence of P1 centers in detonation nanodiamond crystals has been indirectly demonstrated. The authors discuss the nature and distribution of spins as observed by the electron paramagnetic resonance, the composition of phases and size of the coherent scattering region, and crystal density (calculated by the X-ray method) of the detonation nanodiamond samples at hand.

In recent years, detonation nanodiamond is regarded as a promising material for biomedical applications. However, a significant problem that stops of intensive development of this area is a absence of commercial NDs standardization. This article presents the results of the study of physicochemical properties of several industrial nanodiamonds available in the international market. The differences of physicochemical characteristics of nanodiamonds produced, selected and purified in various ways are shown. A method is developed for industrial processing of nanodiamonds, that represents high-temperature hydrogenation of diamond surface and allows to unify their properties. It is shown that after these processing nanodiamonds have the same surface chemistry and can form stable hydrosols. The proposed method of industrial nanodiamonds unification can become a universal method of its standardization.

This paper describes the use of gamma activation analysis methods for determining impurities in detonation nanodiamonds (DNDs) from different manufacturers, in different probes of the same batch from the same manufacturer, in chemically modified DNDs, and in DND–glycine conjugate. Twelve impurity elements were detected and quantified in DND samples: Cl, Ti, Cr, Fe, Ni, Zr, Mo, Sb, Sr, Mn, U and Eu. The content of impurity elements in DND samples varies from 0.1 to 3wt.%. Considering possible medical applications of DND, compliance with approved maximum permissible concentrations of heavy metals in medicinal agents is required.

Nanodiamond (ND) particles are popular platforms for the immobilization of molecular species. In the present research, enzyme Escherichia coli inorganic pyrophosphatase (PPase) was immobilized on detonation ND through covalent or noncovalent bonding and its enzymatic activity was characterized. Factors affecting adsorption of PPase such as ND size and surface chemistry were studied. The obtained material is a submicron size association of ND particles and protein molecules in approximately equal amounts. Both covalently and noncovalently immobilized PPase retains a significant enzymatic activity (up to 95% of its soluble form) as well as thermostability. The obtained hybrid material has a very high enzyme loading capacity (∼1 mg mg−1) and may be considered as a promising delivery system of biologically active proteinaceous substances, particularly in the treatment of diseases such as calcium pyrophosphate crystal deposition disease and related pathologies. They can also be used as recoverable heterogeneous catalysts in the traditional uses of PPase.