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Start Over Author "Nikolskaya ED" Topic dendrimers
2 results on '"Nikolskaya ED"'

1. [Accumulation of doxorubicin conjugates with dendritic polymer and vector protein in normal and tumor cells in vitro].

Author

Zamulaeva IA, Matchuk ON, Pronyushkina KA, Yabbarov NG, Nikolskaya ED, Orlova NV, Makarenko SA, Zhunina OA, Kondrasheva IG, and Severin ES

Subjects
ATP Binding Cassette Transporter, Subfamily B biosynthesis, Adenocarcinoma metabolism, Adenocarcinoma pathology, Breast Neoplasms metabolism, Breast Neoplasms pathology, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, MCF-7 Cells, Neoplasm Proteins biosynthesis, Adenocarcinoma drug therapy, Breast Neoplasms drug therapy, Dendrimers chemistry, Dendrimers pharmacokinetics, Dendrimers pharmacology, Doxorubicin chemistry, Doxorubicin pharmacokinetics, Doxorubicin pharmacology, Drug Carriers chemistry, Drug Carriers pharmacokinetics, Drug Carriers pharmacology, alpha-Fetoproteins chemistry, alpha-Fetoproteins pharmacokinetics, alpha-Fetoproteins pharmacology
Abstract

Accumulation of doxorubicin (Dox), its conjugates with the second generation dendritic polymer (G2-Dox) and vector pro- tein (recombinant third domain of alpha-fetoprotein - 3D-G2- Dox) in normal and tumor cells was studied in vitro within the framework of the development of selective transport system of anticancer drugs to the target cells. The objects of the study were cells of peripheral blood mononuclear fraction of healthy donors and cells of breast adenocarcinoma lines MCF-7 and MCF-7/MDR1, differing in chemosensitivity. G2-Dox and 3D-G2-Dox accumulated in tumor cells of the both lines better than free Dox (p<0,05). However removal of these drugs out of cells MCF-7 and MCF-7/MDR1 was significantly different: in the latter case all free Dox was excluded from the cells for 24 hours while Dox, accumulated in composition with dendrimers, still remained in the cells. It was important that 3D-G2-Dox (unlike the G2-Dox) accumulated in normal cells worse than free Dox (p<0.01). Thus, the results indicate that the use of 3D-G2-Dox is the most promising because it accumulates in tumor cells better and in normal cells worse than free Dox. Furthermore it can be assumed that the use of 3D-G2-Dox would be especially useful in cases of multi-drug resistance associated with the high expression of P-glycoprotein.

Published
2016

2. [The Combined Effects of Ionizing Radiation and Dendritic Polymers Loaded with Doxorubicin on the MCF-7 Breast Cancer Cell Line].

Author

Zamulaeva IA, Pronyushkina KA, Matchuk ON, Yabbarov NG, Nikolskaya ED, and Kondrasheva IG

Subjects
Antibiotics, Antineoplastic administration & dosage, Antibiotics, Antineoplastic pharmacokinetics, Cell Culture Techniques, Dose-Response Relationship, Drug, Doxorubicin administration & dosage, Doxorubicin pharmacokinetics, G2 Phase drug effects, G2 Phase radiation effects, Humans, MCF-7 Cells, Antibiotics, Antineoplastic pharmacology, Cell Proliferation drug effects, Cell Proliferation radiation effects, Dendrimers chemistry, Doxorubicin pharmacology, Drug Carriers chemistry, Endocytosis drug effects, Endocytosis radiation effects, Radiation, Ionizing
Abstract

The dendritic polymers (dendrimers) are perspective nanocontainers for transportation of anticancer drugs into cells and a controlled release of the delivered substances. However, the combined effect of ionizing radiation and dendrimers loaded with anticancer drugs has been poorly studied and is the aim of this research. We used poliamidoamin (PAMAM) dendrimers of the second generation (G2) covalently conjugated with doxorubicin (Dox) via an acid labile linker, cis-aconitic anhydride. We compared the intracellular accumulation of Dox and growth rate of the MCF-7 cell culture under the single and combined action of ionizing radiation at a dose of 4 Gy, free Dox and G2-Dox. It was found that within 2 hours free Dox accumulated in cancer cells better than Dox connected with G2 dendrimers (p < 0.05 in the concentration range of 1-5 μmol/l). The intracellular accumulation of Dox was higher by 1.7 times for the free Dox than that connected with dendrimers (for concentration 0.5 μmol/l p = 0.02) after 26 hours of incubation. Like the intracellular accumulation of Dox, inhibition of the cell culture growth was more pronounced when using free Dox than G2-Dox in the case of both a single and combined action of these drugs. Subadditivity effects of the combined action of both drugs and ionizing radiation are shown in terms of reducing the number of tumor cells 24 hours after irradiation. The results indicate the need for further development of selective delivery systems for Doxin tumor cells, providing a more intense accumulation of anticancer drug in target cells.

Published
2015

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