Activatable chemiluminescence enabled external-light-free photodynamic therapy: From mechanisms, structural designs to theranostics

Abstract

Photodynamic therapy (PDT) is a noninvasive, clinically approved technique used to treat various conditions, including bacterial infections, several skin diseases, and cancers. It typically undergoes the external-light-irradiation of a specific photosensitizer to generate reactive oxygen species. These species cause damage to surrounding tissue and lead to cell death. However, the limited penetration depth of external light through biological tissues significantly restricts the effectiveness of PDT for deep lesions and tissues. Chemiluminescence (CL) is an emission phenomenon triggered by a chemical reaction, rather than by light excitation as is the case with conventional fluorescence. The construction of CL-initiated PDT agents provides a potential external-light-irradiation-free approach for deep-tissue PDT. Significant advances have recently been achieved in the construction of CL-initiated nano- and molecular-PDT agents through either noncovalent or covalent combination of the CL unit with the photosensitizer. This review highlights recent advancements in CL-mediated PDT for bioimaging and tumor treatment, discussing the underlying mechanisms, structural design principles, and results from in vitro cellular and in vivo animal investigations. Moreover, the current challenges and future outlook for CL-mediated PDT in tumor theranostics are also discussed.