Cell-Molecular Interactions of Nano- and Microparticles in Dental Implantology.

The role of metallic nano- and microparticles in the development of inflammation has not yet been investigated. Soft tissue biopsy specimens of the bone bed taken during surgical revisions, as well as supernatants obtained from the surface of the orthopedic structures and dental implants (control), were examined. Investigations were performed using X-ray microtomography, X-ray fluorescence analysis, and scanning electron microscopy. Histological studies of the bone bed tissues were performed. Nanoscale and microscale metallic particles were identified as participants in the inflammatory process in tissues. Supernatants containing nanoscale particles were obtained from the surfaces of 20 units of new dental implants. Early and late apoptosis and necrosis of immunocompetent cells after co-culture and induction by lipopolysaccharide and human venous blood serum were studied in an experiment with staging on the THP-1 (human monocytic) cell line using visualizing cytometry. As a result, it was found that nano- and microparticles emitted from the surface of the oxide layer of medical devices impregnated soft tissue biopsy specimens. By using different methods to analyze the cell-molecule interactions of nano- and microparticles both from a clinical perspective and an experimental research perspective, the possibility of forming a chronic immunopathological endogenous inflammatory process with an autoimmune component in the tissues was revealed.

Immunopathological Inflammation in the Evolution of Mucositis and Peri-Implantitis.

The purpose of this study was to provide an immuno-mediated substantiation of the etiopathogenesis of mucositis and peri-implantitis based on the results of experimental, laboratory and clinical studies. The biopsy material was studied to identify impregnated nanoscale and microscale particles in the structure of pathological tissues by using X-ray microtomography and X-ray fluorescence analyses. Electron microscopy with energy-dispersive analysis identified the composition of supernatants containing nanoscale metal particles obtained from the surfaces of dental implants. The parameters of the nanoscale particles were determined by dynamic light scattering. Flow cytometry was used to study the effect of nanoscale particles on the ability to induce the activation and apoptosis of immunocompetent cells depending on the particles' concentrations during cultivation with the monocytic cell line THP-1 with the addition of inductors. An analysis of the laboratory results suggested the presence of dose-dependent activation, as well as early and late apoptosis of the immunocompetent cells. Activation and early and late apoptosis of a monocytic cell line when THP-1 was co-cultured with nanoscale metal particles in supernatants were shown for the first time. When human venous blood plasma was added, both activation and early and late apoptosis had a dose-dependent effect and differed from those of the control groups.

Doxorubicin-Loaded Core-Shell UiO-66@SiO2 Metal-Organic Frameworks for Targeted Cellular Uptake and Cancer Treatment.

Beneficial features of biocompatible high-capacity UiO-66 nanoparticles, mesoporous SiO2, and folate-conjugated pluronic F127 were combined to prepare the core-shell UiO-66@SiO2/F127-FA drug delivery carrier for targeted cellular uptake in cancer treatment. UiO-66 and UiO-66-NH2 nanoparticles with a narrow size and shape distribution were used to form a series of core-shell MOF@SiO2 structures. The duration of silanization was varied to change the thickness of the SiO2 shell, revealing a nonlinear dependence that was attributed to silicon penetration into the porous MOF structure. Doxorubicin encapsulation showed a similar final loading of 5.6 wt % for both uncoated and silica-coated particles, demonstrating the potential of the nanocomposite's application in small molecule delivery. Silica coating improved the colloidal stability of the composites in a number of model physiological media, enabled grafting of target molecules to the surface, and prevented an uncontrolled release of their cargo, with the drawback of decreased overall porosity. Further modification of the particles with the conjugate of pluronic and folic acid was performed to improve the biocompatibility, prolong the blood circulation time, and target the encapsulated drug to the folate-expressing cancer cells. The final DOX-loaded UiO-66@SiO2/F127-FA nanoparticles were subjected to properties characterization and in vitro evaluation, including studies of internalization into cells and antitumor activity. Two cell lines were used: MCF-7 breast cancer cells, which have overexpressed folate receptors on the cell membranes, and RAW 264.7 macrophages without folate overexpression. These findings will provide a potential delivery system for DOX and increase the practical value of MOFs.