Rationally designed monoamine oxidase A‐activatable AIE molecular photosensitizer for the specific imaging and cellular therapy of tumors

Abstract Due to both the requirements of repeated complex organic synthesis and tedious biochemical verification experiments for the screening of new photosensitizers, the development of a satisfactory photosensitizer with excellent photosensitivity and highly specific response ability is still a great challenge for the accurate imaging localization and the precise photodynamic therapy (PDT) of tumors. Herein, under the help of theoretical calculations, a high‐efficient target‐activatable aggregation‐induced emission (AIE) molecular photosensitizer, TPE‐TThPy, is rationally designed and synthesized by the conjugation of tetraphenylethylene (TPE, which is used as the electron donor) and tetrahydropyridine (ThPy, which can be converted to methylpyridine salts as the electron acceptor) using thiophene (T) as the π‐bridge. This TPE‐TThPy molecule exhibits not only good cellular uptake and mitochondrial targeting ability but also ultra‐high monoamine oxidase A (MAO‐A) response specificity and excellent photosensitivity when oxidized under the action of MAO‐A. The specifically imaging ability and cellular PDT performance of the MOA‐A‐activatable AIE photosensitizer of TPE‐TThPy is demonstrated by using different cell lines and mouse tumor models. The successful development of this MOA‐A‐activatable AIE photosensitizer also provides insight for the development of single‐molecule PDT therapeutic drugs with excellent photosensitivity and highly specific targeting‐response ability.