Biodistribution and stability of CdSe core quantum dots in mouse digestive tract following per os administration: advantages of double polymer/silica coated nanocrystals.

CdSe-core, ZnS-capped semiconductor quantum dots (QDs) are of great potential for biomedical applications. However, applications in the gastrointestinal tract for in vivo imaging and therapeutic purposes are hampered by their sensitivity to acidic environments and potential toxicity. Here we report the use of coatings with a combination of polythiol ligands and silica shell (QDs PolyT-APS) to stabilize QDs fluorescence under acidic conditions. We demonstrated the stability of water-soluble QDs PolyT-APS both in vitro, in strong acidic solutions, and in vivo. The biodistribution, stability and photoluminescence properties of QDs in the gastrointestinal tract of mice after per os administration were assessed. We demonstrated that QDs coated with current traditional materials - mercapto compounds (QDs MPA) and pendant thiol group (QDs PolyT) - are not capable of protecting QDs from chemically induced degradation and surface modification. Polythiol ligands and silica shell quantum dots (QDs PolyT-APS) are suitable for biological and biomedical applications in the gastrointestinal tract.

Influence of the substitution of 3-vinyl by 3-formyl group on the photodynamic properties of chlorin P6: molecular, cellular and in vivo studies.

Molecular in vitro and in vivo properties of 3-devinyl-3-formylchlorin p6 (FCp6) were examined in order to characterize this derivative as a new prospective photosensitizer. The long-wavelength absorption maximum of FCp6 was 690-696 nm (depending on environment). FCp6 was found to bind readily to membranous structures and form complexes with some proteins. The dye was associated with the plasmalemma and distributed rather diffusely along the cytoplasm with ca a three-fold higher accumulation within mitochondria in A549 human adenocarcinoma cells. The spectral analysis revealed that the major part of FCp6 was bound to membranes within cells. The membrane-bound FCp6 was shown to generate singlet oxygen efficiently. The average cytoplasmic concentration of FCp6 in A549 cells achieved ca 80% of its extracellular concentration in complete medium. The dye was characterized by a very fast efflux (16-fold decrease in 2 h). The ex vivo analysis of FCp6 fluorescence in mice revealed that the maximal dye content in blood, tissues, organs and tumor was achieved in less than 1 h after injection, followed by a considerable (ca six-fold) decrease during the next 23 h and a long-term persistence at low level. A preferential accumulation of FCp6 in subcutaneously implanted Ehrlich carcinoma along with its higher retention level comparing to the surrounding skin and muscles were observed in mice treated with different dye doses. In vitro cytotoxic assays with A549 and Raji B-cell lymphoma cells as well as in vivo analyses using Ehrlich carcinoma in mice revealed the very low toxicity of FCp6 without light irradiation and the significant photodynamic activity of this compound.

[Pharmacokinetics of human milk lactoferrin in intact mice and tumor-carrying animals]. / Izuchenie farmakokinetiki laktoferrina zhenskogo moloka u intaktnykh myshei i zhivotnykh-opukholenositelei.

Pharmacokinetics of iodine containing and native lactoferrin from human milk was studied in intact mice and the animals with Ehrlich ascites carcinoma. Both these antigens, native and I-lactoferrin, were similarly distributed in intact mice body. The same pharmacokinetics was found in tumor-bearing animals. Exogenous lactoferrin penetrated mainly into liver tissue, then simultaneously with bile--into small intestine and further into large intestine. Distinct accumulation of the glycoprotein was not found in tumor tissue.

[An immunohistochemical study using monoclonal antibodies of the antigen of fat globule membranes in human milk]. / Immunogistokhimicheskoe izuchenie antigena membran zhirovykh globul zhenskogo moloka s pomoshch'iu monoklonal'nykh antitel.

Monoclonal antibodies (Mab) IKO-21 and IKO-25 obtained to the membrane antigen of the woman milk lipid globules were tested immuno- and cytochemically on the samples of human normal definitive and embryonal tissues and tumours. Mab IKO-21 are shown to react, apart from epithelial tissues, with a vascular endothelium and blood cells. Mab IKO-25 are specific to the epithelial tissue and malignant epithelial tumours. Their intensive reaction with the cells of malignant tumours of the mammary gland, lung, ovary and the type of their distribution in the organs and tissues enables their use in the differential diagnosis of malignant epithelial and non-epithelial tumours as for revealing metastases both in vitro and in vivo.

[Molecular mechanism of hemosorption]. / K voprosu o molekuliarnykh mekhanizmakh deistviia gemosorbtsii.

Several humoral and intracellular components of blood were investigated in patients with esophageal carcinoma treated with preventive hemosorption + chemotherapy, and also in patients with purulent complications after surgery before hemosorption, during hemosorption and 3 hrs, 1, 3 and 7 days after hemosorption. It was demonstrated that during hemosorption and in the first days following it no significant changes occurred either in blood count or in protein content, protein composition, levels of alpha 1-AT, IgG, IgA and IgM in blood plasma. Preventive hemosorption did not cause hypo- or dysproteinemias in these patients. Hemosorption led to normalization of certain biochemical indices of blood: increase in BAEE activity and decrease in the level of middle molecular toxins, which indicated the reduction of endotoxicosis in patients. During hemosorption there was a marked (100-200 times) increase in blood plasma of lactoferrin, which is a component of specific granules in neutrophils. It is assumed that the leading modifying mechanism of action of hemosorption is an output of physiologically active components the main of which is lactoferrin.

[Study of the integral antigen of the membranes of fatty globules of human milk]. / Izuchenie integral'nogo antigena membran zhirovykh globul zhenskogo moloka.

The glycoprotein with the molecular weight of 82,500 D (Ag3) was extracted from the native membranes of fatty globules of human milk and was purified by isoelectrofocusing. Polyclonal antisera (PCA) as well as monoclonal antibodies (MoAb)-ICO-21, ICO-22, ICO-26, ICO-29 against this membrane antigen were produced. The localization of the antigen in the human normal and malignant tissues was tested by the immunochemical technique. Apical staining of the Ag3 was in the acinus and duct cells of the normal breast. Weak staining with the antibodies to Ag3 was revealed in the epithelium cells of ovaries, bronchi, kidney tubules and uterine tubes. The far more pronounced staining of the Ag3 with PCA and MCA was observed in the cell cytoplasma both in the primary and metastatic breast and ovarian tumours. The specificity of the MoAb to Ags suggests that they will be useful in the diagnosis of the malignant disease of the breast and ovary.

[Immunohistochemical detection of lactoferrin of human milk in the tissues of the human and the fetus]. / Immunogistokhimicheskoe vyiavlenie laktoferrina zhenskogo moloka v tkaniakh vzroslogo cheloveka i ploda.

By means of the indirect immunoperoxidase method in deparaffinized slices a comparative investigation on distribution of the female milk lactoferrin (LF) in tissues of the mature person and in the fetus has been performed. LF is revealed in cells of the neutrophil line of the mature person and of the fetus and in the secretory epithelium of some organs of the mature person (in the mammary, submandibular and parotid salivary glands, in the bronchial mucous membrane glands in the fundal and pyloric glands of the stomach). In all the cases investigated LF is revealed in the cells producing serous secrete: in the cells of the serous terminal parts and in the serous semilunar mixed terminal parts of the salivary glands, in the serous cells of the bronchial glands and in the chief cells of the gastric mucous membrane glands. In the fetal secretory epithelium of the organs LF is not found. As LF is revealed in the secretory epithelium of the mature person and is not revealed in the corresponding epithelium of the fetus, it should be considered as a marker of the cells, that reach certain degree of differentiation.

[Tolerance of different cell types for hypotonic action]. / Ustoichivost' raznykh tipov kletok k deistviiu gipotonii.

The behavior of cells with different structure of cytoskeleton was studied in the hypotonic media: protoplasts, embryonal mouse fibroblasts and transformed mouse fibroblasts (L-line). Protoplasts were most sensitive to the hypotonic media. They began to disrupt in the hypotonic medium 4:1, and in the hypotonic medium 1:7 a complete lysis of cells was observed. Transformed mouse fibroblasts were disrupted in the medium diluted 1:15, while embryonal mouse fibroblasts were not disrupted in the medium diluted 1:31. Moreover, in the hypotonic conditions an essential difference was observed between the cells studied. Embryonal mouse fibroblasts are more tolerant to the hypotonic conditions than L-cells and protoplasts. It is suggested that the cytoskeleton may define the cell tolerance in hypotonic media.

[Immunohistological study of the normal human gastric mucosa and that of chronic gastritis]. / Immunogistologicheskoe izuchenie slizistoi obolochki zheludka cheloveka v norme i pri khronicheskom gastrite.

Normal gastric mucosa and that in atrophic gastritis was studied by indirect immunoperoxidase method. Intestinal antigens CEA and beta 1MA were found in the foetal stomach and in the foci of intestinal metaplasia with and without dysplastic epithelial changes. Gastric antigens, pepsinogens of the foetal and 2-nd type, were found in foetal and adult stomach, as well as in the foci of intestinal metaplasia with dysplastic changes. The discovery of concomitant presence of gastric and colonic antigens in the dysplastic epithelium may indicate the existence of pluripotent stem cells capable of differentiation in the direction of gastric glandular epithelium, and in the direction of enterocytes. The possibility is suggested of origination of gastric carcinoma of different histologic structure from intestinal metaplasia with dysplastic changes.