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

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)/C] are investigated analyzing the differences with the analogous C 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 has a 2:1 stoichiometry, the same as C, 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 forming a relatively stable complex by interacting through their primary rims, however exposing part of C 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 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.