ANTICANCER ACTIVITY OF DOXORUBICIN CONJUGATES WITH DENDRITIC POLYMERS OF SECOND GENERATION AND VECTOR PROTEIN IN MODEL SYSTEMS IN VITRO AND IN VIVO

Abstract

Anticancer activity of doxorubicin (Dox), its conjugates with the second generation dendritic polymer (G2-Dox) and vector protein (recombinant third domain of alpha-fetoprotein - 3D-G2-Dox were studied in vitro and in vivo within the framework of the development of selective transport system of anticancer drugs to the target cells. The objects of the study were MCF-7 and MCF-7/MDR1 breast cancer cells, differing in chemosensitivity as well as mouse melanoma line B16. Anticancer activity of G2-Dox and 3D-G2-Dox was demonstrated in vivo (for B16 melanoma) and in vitro (for chemoresistant MCF-7/MDR1 cells, expressing P-glycoprotein). The effectiveness of anticancer action of G2-Dox and 3D-G2-Dox did not differ from that for free Dox. However for chemosensitive line MCF-7 free Dox proved to be more effective drug. It is important that the conjugates, and particularly 3D-G2-Dox, accumulated much weaker than the free Dox in normal cells isolated from bone marrow, spleen and liver of mice. The findings suggest that the main benefit from the possible use of such conjugates can be associated with reduced toxic effect of Dox on normal tissues and organs.