Influence of the doxorubicin conjugated PAMAM dendrimer surface charge on cytotoxic effects and intracellular trafficking routes in tumor cells

Dendritic polymers have a huge potential as a molecular cargoes with targeting abilities in diagnosis and treatment of cancer. The amine-terminated (16 primary amino-groups) and acetyl-terminated (14 primary amino-groups out of 16 were blocked) 2nd generation PAMAM dendrimers (G2 and G2(ac) respectively) were conjugated with doxorubicin (Dox) and absorbed by the cells with different efficiency. G2(ac)-Dox characterized much slower internalization rate than G2-Dox. At the same time G2ac showed partial colocalization with lysosomal marker LAMP2 after 4 h of incubation. G2(ac)-Dox conjugate demonstrated much higher cytotoxic activity against sensitive to Dox SKOV3 and resistant SKVLB cells than amine terminated G2-Dox conjugate. The results obtained indicate cellular internalization pathways dependence on the nature and charge of surface chemical groups of dendrimers used. (C) 2017 Elsevier Ltd. All rights reserved.