Thermally Activated Delayed Fluorescence‐Guided Photodynamic Therapy Through Skeleton‐Homologous Nanoparticles: a Rational Material Design for High‐Efficient and High‐Contrast Theranostics

Abstract Although photoluminescence imaging‐guided photodynamic therapy (PDT) is promising for theranostics, it easily suffers from tissue autofluorescence and PDT photoproducts. To develop time‐resolved imaging (TRI)‐guided PDT with long‐lived emission pathways, like thermally activated delayed fluorescence (TADF), is urgent but challenging, because of the triplet competition between radiative transition and reactive oxygen species (ROS) production. Herein, skeleton‐homologous nanoparticles are designed and constructed to address this dilemma, thereby achieving in vivo TRI‐guided PDT for the first time. This system is formed with a lipophilic TADF core (as a TRI probe) encapsulated by an amphiphilic photosensitizer shell (as the corona exposed to oxygen for PDT), both of which are derived from the same donor–acceptor skeleton to minimize phase separation in the single entity, and enable the same long‐wavelength photoexcitation for TRI and PDT. The chloropropylamine group is helpful for endoplasmic reticulum targeting to enhance PDT upon minimizing the ROS transmission path. Synchronously, the TADF core exhibits a delayed fluorescence of 40 µs for a clear TRI. The NPs are eventually applied in vivo with a high signal‐to‐background ratio (45.25) and outstanding PDT effects in a mouse model of deep‐seated kidney cancer. Such a material design is beneficial for developing high‐efficient and high‐contrast theranostic approaches.