Type I photodynamic antimicrobial therapy: Principles, progress, and future perspectives

The emergence of drug-resistant bacteria has significantly diminished the efficacy of existing antibiotics in the treatment of bacterial infections. Consequently, the need for finding a strategy capable of effectively combating bacterial infections has become increasingly urgent. Photodynamic therapy (PDT) is considered one of the most promising emerging antibacterial strategies due to its non-invasiveness, low adverse effect, and the fact that it does not lead to the development of drug resistance. However, bacteria at the infection sites often exist in the form of biofilm instead of the planktonic form, resulting in a hypoxic microenvironment. This phenomenon compromises the treatment outcome of oxygen-dependent type-II PDT. Compared to type-II PDT, type-I PDT is not constrained by the oxygen concentration in the infected tissues. Therefore, in the treatment of bacterial infections, type-I PDT exhibits significant advantages over type-II PDT. In this review, we first introduce the fundamental principles of type-I PDT in details, including its physicochemical properties and how it generates reactive oxygen species (ROS). Next, we explore several specific antimicrobial mechanisms utilized by type-I PDT and summarize the recent applications of type-I PDT in antimicrobial treatment. Finally, the limitations and future development directions of type-I photosensitizers are discussed.