Advancements in photodynamic therapy for tuberculosis treatment.

The emergence of drug-resistant strains of Mycobacterium tuberculosis (Mtb), coupled with lengthy treatment cycles and adverse side effects of traditional therapies, poses a significant global challenge in the form of tuberculosis (TB). Photodynamic therapy (PDT) generates reactive oxygen species that target specific tissues or cells via light irradiation at specific wavelengths. It directly disrupts critical structures and components of Mtb to exert its anti-TB effects. Unlike traditional antibiotics that rely on specific targets for efficacy, PDT prevents the occurrence of drug resistance at the mechanism level. Moreover, research indicates that multiple photosensitizers (such as methylene blue and porphyrin derivatives) demonstrate significant bactericidal effects against both drug-sensitive and drug-resistant Mycobacterium tuberculosis in vitro. It can also serve as an adjunct to conventional anti-TB drugs to improve therapeutic efficacy. However, tuberculosis infections predominantly occur in the deep tissues of the lungs. Achieving precise targeted delivery of photosensitizers to the lungs and ensuring their effective activation at deep infection sites, while overcoming the technical limitations of light sources-namely their limited excitation capacity and difficulty in effectively reaching deep pulmonary tuberculosis lesions-has become the core bottleneck for the clinical translation and application of this therapy. In this review, we discuss the principles and mechanisms of PDT, explore the structural characteristics and anti-infective capabilities of various photosensitizers. Finally, we discuss its current clinical applications in tuberculosis patients and future potential, offering novel perspectives for tuberculosis treatment.