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The Role of Transition Metals and Irradiation in the Action of Anticancer Drug Camptothecin
Klaudia Jomová, Marián Valko
Slovakia

The anticancer drug camptothecin (CPT) is a plant alkaloid that is very effective in the treatment of gastrointestinal tumours. Several clinically important derivatives of CPT have been also synthesized; the most recent involve topotecan and irinotecan. The anticancer activity of CPT family of drugs is dependent on the maintenance of the lactone ring in the closed form (ring E) (Figure 1).



We investigated whether the transition metal ions, namely copper could support the efficient encapsulation of irinotecan into liposomes and stabilize the biologically active lactone form of the drug. The 1,2-distearoyl-sn-glycero phosphocholine/cholesterol (60:40 mol%) liposomes formulated with 350 mM copper chloride exhibited >95% irinotecan loading after a 10 min incubation at 45 oC. The irinotecan loading has been further supported by Cryo- Transmission Electron Microscopy. Irinotecan and topotecan encapsulated in liposomes, were found to exist mainly in the therapeutically active lactone form (90% and 92% of the total drug, respectively).

In addition, we studied the photochemical properties of CPT in the presence of various metal ions. The EPR spin trapping experiments indicate that CPT is a promising photosensitizer and that free radicals and singlet oxygen generated upon illumination of CPT play a key role in DNA cleavage in cancer cells.