A Study of the Photo-sensitized Oxidative Activation of Indole-3-Acetic Acid as an Anti-Cancer Photodynamic Therapy

While the standard treatments for solid tumors are surgery, radiation therapy and chemotherapy, an alternative treatment modality known as photodynamic therapy (PDT) has become increasingly important in recent years due to its highly precise tumor- targeting capability, particularly towards small-sized tumors where surgical treatment can be difficult. In PDT, a non-toxic drug precursor, called a sensitizer, is administered into the patient’s body and allowed to accumulate inside the tumor. When the tumor is irradiated by a precisely targeted laser light, the sensitizer, by the action of light, produces a toxic substance which then kills the cancer cells. However, similar to radiation therapy, most PDT sensitizers, known as type II sensitizers, used clinically, require the target (tumor) tissue to be well-oxygenated in order to achieve their best anti- cancer effects. But recent discovery showed that most solid tumors contain regions that are poorly oxygenated, therefore compromising the eradication efficacy of these treatments. In this proposed work, we intend to develop some novel PDT sensitizers, known as type I sensitizers, which do not require oxygen for their anti-cancer activities, for the treatment of solid tumors. Our proposed therapeutic strategy involves the use of a plant hormone, called indole-3-acetic acid (IAA) and its analogs, as a non-toxic drug partner to the type I sensitizers. Upon irradiation with appropriate wavelength of light, IAA will be converted by the type I sensitizers to a toxic drug which kills the cancer cells inside the solid tumor. This treatment strategy will be evaluated using human nasopharyngeal carcinoma cells as model. The underlying chemistry of this treatment strategy will also be explored for further improvement of this therapeutic method.