Drug targeting in cancer: targeting photosensitizers in photodynamic therapy

The targeted delivery of chemotherapeutic agents to defined cells, either stromal or cancer cells, in cancer lesions is one of the main challenge and a very active field of research in the development of treatment strategies to minimize side-effects of drugs, including in photodynamic detection and therapy (PDT) of cancer. PDT involves the detection and destruction of diseased tissue by visible light after loading of the target tissue with a photosensitizer. In PDT the general distribution to the whole body of the photosensitizers results in important side-effects, such as generalized photosensitization, and poor acceptance of treatments by the patients. It is widely accepted that not only tumor cells, but also tumor-associated stromal cells express molecules at their membrane that are different, or are overexpressed, when compared to non-tumoral cells of the same tissue origin. In particular tumor-associated vasculature displays this differential expression, which includes integrins, proteases, receptors for peptidic or glycosidic ligands. Therefore one goal of PDT in the field of cancer is to develop chemically derivatized photosensitizers able to target tumor cells or tumor-associated cells via specific recognition mechanisms, and cancer ablation using laser exposure. This manuscript will review the approaches which have been explored to achieve these goals