Conference Proceeding

Conjugates of PAMAM dendrimers with doxorubicin and vector protein decrease survival of cancer cells demonstrating resistance to traditional anticancer agents in vitro

Ms.Selivanova Elena,
National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Development of new systems for selective transport оf anticancer agents in tumor cells on the base of dendritic polymers (dendrimers) is appeared to be one of the most effective approaches to overcome cancer chemo resistance associated with the existence of cancer stem cells (CSCs) and multidrug resistance (MDR). The aim of this work was to study cytotoxic effects of polyamideamine dendrimers of the second generation (G2) covalently conjugated to doxorubicin (Dox) and a vector protein (the third recombinant domain of the alpha-fetoprotein - 3D AFP) on two breast cancer cell lines (MCF-7 and MCF-7/MDR1) differing in sensitivity to anticancer drugs and to compare sensitivity of CSCs and non-CSCs to these conjugates. The cytotoxic effects were assessed after incubation with free Dox, G2-Dox and 3D-G2-Dox at concentration of 2.5 µm for Dox using clonogenic test. CSCs were identified in MCF-7 line by flow cytometry as side population of Hoescht33342-excluding cells 24 hours after incubation with these agents. 3D-G2-Dox significantly decreased the clonogenity of MCF-7/MDR1 cells (19% in comparison to control, p<0.05) in contrast to the MCF-7 cells (70%). Free Dox was effective for elimination only MCF-7 cells (1%, p<0.001), but not MCF-7/MDR cells (78%). In addition, 3D-G2-Dox was able to decrease the proportion of MCF-7 CSCs in contrast to free Dox that greatly increased the proportion of such cells. The results show promising use of dendrimers as nano-carriers of anticancer drugs for overcome tumor cell chemo resistance.

Published: 12 May 2017