Correlation of the in vitro biological effect with physico-chemical parameters of doxorubicin binding with fullerene conjugates

Here, we report a quantitative correlation between the relative biological effect in the HeLa tumor cell line induced by a mixture of the anticancer antibiotic doxorubicin (DOX) with various fullerene compounds (FC), and the equilibrium DOX-FC binding constant. These results indicate that complexation of DOX with FC molecules is likely the primary physico-chemical reason (at least in part) for the observed biological synergy, and that this mechanism should always be taken into account in in vitro/in vivo studies when DNA-binding drugs and carbon nanoparticles are present simultaneously in biological media. We also report a new combined DLS-UV/Vis approach to measure drug-fullerene equilibrium binding constants under conditions in which the main fraction of FC molecules exists in an aggregated state, requiring knowledge of the distribution of various clusters by their size.