Cytotoxic effects of the combined action of ionizing radiation and doxorubicin conjugates with dendritic polymer and a vector protein to tumor cells in vitro

The dendritic polymers (dendrimers) are perspective nanocontainers for targeted transport of anticancer drugs to the target cells. However, the combined effect of ionizing radiation and the dendrimers conjugated with anticancer drugs and vector molecules, are virtually unexplored, so this is the main goal of the study. We used polyamideamine (PAMAM) dendrimers of the second generation (G2), covalently conjugated with doxorubicin (Dox) and a vector protein (alpha-fetoprotein recombinant third domain - 3D).The cytotoxic effects and intracellular accumulation of Dox were studied after 24 hours of incubation of the cells (breast adenocarcinoma MCF-7 and MCF-7/MDR1 cells) with free Dox, unmodified G2 dendrimers, loaded with Dox (G2-Dox), or conjugates of dendrimers with the vector protein and Dox (3D-G2-Dox) only or in combination with ionizing radiation. For MCF-7 line using Dox conjugates with dendrimers in combination to irradiation was not effective because conjugates did not increase the cytotoxic effects of radiation exposure. For MCF-7/MDR1 line synergistic effects were shown after the combined treatment with G2-Dox or 3D-G2-Dox with dendrimers and radiation. Thus, in terms of overall cytotoxic effects on stable tumor cell lines, using the studied conjugates of Dox with dendrimers is justified only in combination with irradiation and only in the case of high expression of P-glycoprotein, which determines the multidrug resistance of cancer cell line MCF-7/MDR1.