Photodynamic therapy comes of age

The concept underlying photodynamic therapy (PDT) is the use of light-absorbing molecules which, when delivered to target cells, and activated by irradiation with light of the appropriate wavelength, produce reactive oxygen species that cause cell death by apoptosis or necrosis. Classically, photodynamic agents have been macrocycles and, as such, application is limited to topical and intravenous administration. In the latter case, reliance has been placed on the characteristic behavior of the photodynamic agents in showing some degree of selectivity for concentrating in the target to minimize non-specific damage to the host tissue. The parameters open to development of improved drugs are: (i) the design of the photodynamic agent molecule as a means of determining the wavelength of light for activation, and for influencing physicochemical characteristics and the pharmacokinetic behavior of the drug; (ii) the delay between administration and activation; (iii) the nature of the activating light source; and, (iv) the duration and intensity of the activating light. Obviously, PDT is attractive for treating disease states in which natural apoptotic mechanisms are compromised, specifically for cancerous states and in cases of uncontrolled cell proliferation. PDT also has immunomodulatory sequelae, including triggering of T-cell mediated activity against residual cancerous cells. The use of PDT is being extended to diverse, related immune and proliferative disease states, and to the inactivation of bacteria and viruses. Increasingly, attention is being given to improving treatment by targeting conjugates and local delivery strategies, as well as by the design of photodynamic agents with closely defined photophysical and physicochemical properties. Progress is being made in challenging indications, such as the treatment of solid and pigmented tumors. Alternative technologies not involving light activation are available for some molecules which may also be used with light activation. Some ex vivo techniques and medical devices have been reported.