Angewandte Chemie International Edition
© WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
For full article and contact information, see Angew. Chem. Int. Ed. 1999, 38 (10), 1460 - 1463
Can Light and Platinum Fight Cancer?
A new, light-activated version of the agent cisplatin
could make cancer therapy more efficient
The medicines, such as the important metal complex cisplatin, that doctors employ in the battle against cancer often attack more than the tumor. The side effects of chemotherapy - for example loss of hair and appetite - come from the fact that the active agents are more likely to indiscriminately attack all fast-growing cells in the body. One solution to this could be medications that are targeted to act only on the tumor - in that they are only activated by light once they are "on the spot." A team working with Edinburgh chemist Peter J. Sadler has now introduced a chemical compound that works like cisplatin, but is first "triggered" by light.
The idea of controlling the attack of agents on tumors using light is not new. For example, there are already substances that transfer the energy from light, which is channeled to the tumor through glass fibers, to the oxygen molecules present in small quantities in the cell. Activated in this manner, these then destroy the DNA of the illuminated cell. The agent cisplatin works in a different way: it binds tightly to the DNA and prevents the cell from reading the genetic information stored in its DNA molecule - unfortunately this does not only take place in tumors.
Here is where the new variant of cisplatin, which Sadler and his co-workers have prepared, puts things right: it consists of a compound of platinum that releases a cisplatin-like compound only when irradiated with light. This compound then settles, as shown by trial experiments, into the DNA in a fashion similar to the known agent. Advantage of the new substance: it doesn't require oxygen for selective reaction. In addition, in contrast to cisplatin, it docks in two places on the DNA when irradiated, giving the tumor cell less opportunity to gear up for attack.
Sadler and his team have also found possibilities for controlling the activity of the agent: depending on the composition of some of the groups of atoms bound by the cisplatin, the tumor "poison" is activated more slowly or quickly when irradiated. Sadler hopes to get rid of one of the remaining disadvantages of his compound in the same way: presently, the substance is so reactive that it would also destroy other molecules in healthy cells.