Exploring the role of phytochemicals as potent natural photosensitizers in photodynamic therapy

Background: Cancer is still considered a deadly disease worldwide due to difficulties in diagnosis, painful treatment procedures, costly therapies, side effects, and cancer relapse. Cancer treatments using conventional methods like chemotherapy and radiotherapy were not convincing due to its posttreatment toxicity in the host. In Photodynamic Therapy (PDT), three individual nontoxic components including a photosensitizer, light source and oxygen cause damage to the cells and tissues when they are combined. Objective: In recent years, phytochemicals are being increasingly recognized as potent complementary drugs for cancer because of its natural availability, less toxicity and therapeutic efficiency in par with commercial drugs. Hence, the idea of using phytochemicals as natural photosensitizers in PDT resulted in a multiple pool of research studies with promising results in preclinical and clinical investigations. Methods: In this review, the potential of phytochemicals to act as natural photosensitizers for PDT, their mode of action, drawbacks, challenges and possible solutions are discussed in detail. Results: In PDT, natural photosensitizers, when used alone or in combination with other photosensitizers, induced cell death by apoptosis and necrosis, increased oxidative stress, altered cancer cell death signaling pathways, increased cytotoxicity and DNA damage in cancer cells. The prooxidant nature of certain antioxidant polyphenols, hormesis phenomenon, Warburg effect and DNA damaging potential plays a significant role in the photosensitizing mechanism of phytochemicals in PDT. Conclusion: This review explores the role of phytochemicals that can act as photosensitizers alone or in combination with PDT and its mechanism of action on different cancers.