Recent Advances and Constructing Strategies of Chemiluminescence- and Bioluminescence-Based Photodynamic Therapy

Photodynamic therapy (PDT) is a noninvasive therapeutic approach for treating cancer and various other diseases. A PDT system relies on three key components: a light source, photosensitizers (PSs), and oxygen. Conventional PDT, which utilizes external light sources to activate PSs, has already been approved for clinical use. However, external light has limited tissue penetration depth and may sometimes cause photoallergic reactions. As a result, internal light sources, such as chemiluminescence (CL) and bioluminescence (BL), have emerged as promising alternatives for future PDT applications. In this review, recent advances in CL/BL-based PDT systems over the past five years are summarized and future trends and design strategies are proposed to guide further research. Specifically, 1) “All-in-one”; 2) covalent linkage; 3) direct PDT for CL-based PDT systems and 1) fusion protein; 2) gene transfection and 3) engineered microorganisms for BL-based PDT systems are discussed. Among these strategies, the “All-in-one” approach—which encapsulates all necessary components within a single delivery system—is possibly the most feasible for optimizing PDT efficacy and the easiest to integrate with chemotherapy or immunotherapy. To advance CL/BL-based PDT toward clinical translation, further evaluation is needed regarding the toxicity and cost of well-designed systems.