Abstract

Photodynamic therapy (PDT) represents an emerging and noninvasive modality that has gained clinical approval for the treatment of cancers, leveraging photosensitizers for optimal therapeutic efficacy. In this study, we synthesized a photosensitizer (denoted as DTCSPP) exhibiting a donor-π-acceptor (D-π-A) structural motif. The DTCSPP manifests aggregation-induced emission (AIE) characteristics, along with good biocompatibility and mitochondrial targeting capabilities attributed to its intrinsic charge and D-π-A architecture. The excited-state intramolecular charge transfer of DTCSPP was systematically investigated in both solution and aggregate states using femtosecond transient absorption spectroscopy (fs-TA). The fs-TA results revealed that DTCSPP exhibited a more rapid and facile excited-state molecular motion in the solution state compared to the aggregate state, implying the predominance of nonradiative decay in its photophysical processes within the solution. Given its ability to simultaneously generate type I and type II reactive oxygen species and induce ferroptosis and autophagy in cancer cells, DTCSPP demonstrates effectiveness in PDT at both cellular and in vivo levels. This study contributes a comprehensive understanding of the excited-state intramolecular charge transfer dynamics of charged D-π-A type AIE photosensitizers, shedding light on their potential application in PDT. The multifaceted capabilities of DTCSPP underscore its promise in advancing the field of anticancer therapeutics, providing valuable insights for the identification of anticancer targets and the development of novel drugs.

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