Recent strategies for developing membrane-targeting photodynamic therapy

Non-invasive and controllable photodynamic therapy (PDT) relying on generating reactive oxygen species (ROS) to selectively kill tumor cells or bacteria, has attracted numerous interests from worldwide researchers in multiple disciplines. To overcome the limited diffusion distance and short lifetime of ROS, subcellular organelle-located PDT has been proposed since it can potentially minimize the spatial gap between ROS and targets. Ultimately, this will decrease the usage concentration of photosensitizers (PSs) and maximize the use of therapeutic agents. Among the organelles, tumor cell membrane as the protective layer for cells controls the substances and energy exchange, while bacterial membrane is the center of bioenergetics and the location of ATP synthesis. Therefore, targeting membrane disruption using PDT could affect the cell or bacteria viability, and achieve the efficient tumor therapy with avoiding endocytosis process. This review provides a comprehensive overview of the existing approaches to membrane-targeted PDT. The membrane-targeting PDT will be discussed according to the different targeting strategies with each section presenting the underlying targeting mechanisms alongside illustrative case studies. Then, the clinic efficacy of new PDT method and its comparison with conventional PDT methods is outlined. This review concludes with an exploration of the challenges and prospects in the design of membrane-targeting PSs. Finally, we outlined some regular patterns and hope to stimulate innovative thinking in PSs research and the advancement of PDT.