Rational Design of Self-Reporting Photosensitizers for Cell Membrane-Targeted Photodynamic Therapy

Organelle-targeted photosensitizers (PSs) have demonstratedenhancedphototherapeutic effect by specifically destroying subcellular organelle.As a critical cellular organelle, the cell membrane plays crucialroles in maintaining cell integrity and regulating cellular communications.To date, a variety of membrane-targeted PSs have been developed andshown exceptional therapeutic effects. However, functional PSs thatcan achieve membrane-targeted photodynamic therapy (PDT) and real-timemonitor the therapeutic process have rarely been reported. In particular,the development of self-reporting PS with near-infrared (NIR) absorptionis highly desirable but remains a challenge. Herein, we presentedtwo molecular rotor-based self-reporting PSs. One of the PSs, MRMP-2, possesses NIR absorption property, making it a promisingcandidate for clinical applications. These PSs could not only enablemembrane-targeted PDT but also demonstrate selective fluorescenceresponse toward viscosity. In this regard, the fluorescence variationof these PSs could be utilized to indicate the disruption of membranestructure during PDT process. By leveraging the feedback of the fluorescencesignal, we could make intuitive judgement about the phototherapeuticresults. As a result, these two PSs possess significant potentialin the field of imaging-guided PDT.