We demonstrate the use of water-soluble C60-β-cyclodextrin conjugates to encapsulate and deliver doxorubicin to the cell nucleus. The behaviour of the fullerene aggregates inside cells is dictated by the functionalization of the C60 cage. While both the C60 conjugates are taken up by lysosomes upon cellular entry, only the one with a hydroxylated cage rapidly escaped the lysosome. The drug delivery system (DDS) with a hydroxylated C60 cage showed significantly enhanced doxorubicin delivery to the cell nucleus, whereas the DDS with a hydrophobic C60 cage was trapped in the lysosome for a longer time and showed significantly reduced doxorubicin delivery to the nucleus. This study opens new paths towards advanced fullerene-based DDSs for small molecule drugs.