A Molecular Dynamics Study of a Photodynamic Sensitizer for Cancer Cells: Inclusion Complexes of γ-Cyclodextrins with C(70)

Photodynamic therapy is an emerging treatment of tumor diseases. The complexes with γ-cyclodextrins (γ-CD) and fullerenes or their derivatives can be used as photosensitizers by direct injection into cancer cells. Using molecular mechanics and molecular dynamics methods, the stability and the geometry of the 2:1 complexes [(γ-CD)(2)/C(70)] are investigated analyzing the differences with the analogous C(60) complexes, studied in a previous theoretical work and experimentally found to be much less efficient in cancer therapy. The inclusion complex of γ-CD and C(70) has a 2:1 stoichiometry, the same as C(60), but is significantly less stable and displays an unlike arrangement. In vacuo, mimicking an apolar solvent, the complex is compact, whereas in water the two γ-CDs encapsulate C(70) forming a relatively stable complex by interacting through their primary rims, however exposing part of C(70) to the solvent. Other higher-energy complexes with the γ-CDs facing different rims can form in water, but in all cases part of the hydrophobic C(70) surface remains exposed to water. The stability and arrangement of these peculiar amphiphilic inclusion complexes having non-covalent interactions in water can be an important key for cancer therapy to enhance both the solubilization and the fullerene insertion into liposomes or cell membranes.