Beyond Photodynamic Therapy:Light-Activated Cancer Chemotherapy

Background: Cancer chemotherapy is limited by severe side effects due to unspecific cytotoxic activity of currently used therapeutics. In order to minimize these unwanted effects, several approaches have been taken, relying on the use of light to activate drugs. As light can be delivered with a very high spatiotemporal resolution, this technique is a promising strategy to selectively activate cytotoxic drugs at their site of action and thus to improve the tolerability and safety of chemotherapy.Objective: This review summarizes different approaches towards photoactivated chemotherapy and identifies its challenges and opportunities.Results: The respective papers were summarized and evaluated in terms of their phototherapeutic indices and the wavelength needed for activation. First, the design, synthesis and/or evaluation of photoactivated metal complexes including platinum-, ruthenium-, and rhodium-complexes is described. Next, photocaged metal complexes and photoacaged organic chemotherapeutics are reported, with a wide range of cytotoxicity mechanisms. The final part includes, examples of photoswitchable drugs for cancer therapy. Some designs, especially metal complexes, stand out due to their very high phototherapeutic index (> 1880) but the common drawback of light-responsive metal complexes and organic chemotherapeutics is the irreversibility of activation. Photoswitchable drugs, however, address this challenge. Nevertheless, the need of UV light for their activation still limits their application.Conclusion: The field of photoactivated cancer chemotherapy is rapidly growing and already includes very promising approaches with designs providing high phototherapeutic indices and also NIR or visible light-activatable drugs.