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

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...

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Bibliographic Details
Published in:	Radiat͡s︡ionnai͡a︡ biologii͡a︡, radioėkologii͡a Vol. 55; no. 6; p. 591
Main Authors:	Zamulaeva, I A, Pronyushkina, K A, Matchuk, O N, Yabbarov, N G, Nikolskaya, E D, Kondrasheva, I G
Format:	Journal Article
Language:	Russian
Published:	Russia (Federation) 01-11-2015
Subjects:	Antibiotics, Antineoplastic - administration & dosage Antibiotics, Antineoplastic - pharmacokinetics Antibiotics, Antineoplastic - pharmacology Cell Culture Techniques Cell Proliferation - drug effects Cell Proliferation - radiation effects Dendrimers - chemistry Dose-Response Relationship, Drug Doxorubicin - administration & dosage Doxorubicin - pharmacokinetics Doxorubicin - pharmacology Drug Carriers - chemistry Endocytosis - drug effects Endocytosis - radiation effects G2 Phase - drug effects G2 Phase - radiation effects Humans MCF-7 Cells Radiation, Ionizing
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Summary:	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.
ISSN:	0869-8031
DOI:	10.7868/s0869803115060132